Nano Letters

The protein corona influences the in vivo biodistribution of ionizable lipid nanoparticles (LNPs) in nucleic acid delivery, yet its structural architecture remains poorly defined. Using cryo-transmission electron microscopy, we visualized LNP-protein interactions in their native state. We show that, unlike the discrete "fuzzy" shells observed on hard nanoparticles, LNPs displayed no peripheral protein shell. Instead, controlled incubation and competitive "dual-particle" assays, supported by molecular dynamics simulations, indicate that LNP membranes undergo localized thickening and electron-dense remodeling consistent with lipoprotein integration rather than surface adsorption. Similar features were observed in extracellular vesicles, suggesting this behavior is shared among lipid-based carriers, and proteomic analysis identified apolipoproteins as the dominant associated proteins. Together, these findings support a model in which the biological identity of LNPs arises through membrane remodeling rather than shell-like adsorption, and provide a framework for the rational design of targeted nanomedicines. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/695162v2_ufig1.gif" ALT="Figure 1"> View larger version (79K): org.highwire.dtl.DTLVardef@5275d3org.highwire.dtl.DTLVardef@1b59ae4org.highwire.dtl.DTLVardef@1cc290eorg.highwire.dtl.DTLVardef@9b7bfb_HPS_FORMAT_FIGEXP M_FIG C_FIG

Direct validation of the nanoscale structural organization of membrane proteins requires localization precision that matches their molecular dimensions. The sodium-potassium pump, or the Na,K-ATPase is an integral membrane protein responsible for maintaining electrochemical gradients and cellular energy homeostasis. Although its crystal structure is characterized, the organization of the Na,K-ATPase within native plasma membranes, particularly whether it forms functional oligomers, remains an open question. Here, we combined 3D MINFLUX nanoscopy with DNA-PAINT with sub-10 nm localization precision to map the clustering topology of the Na,K-ATPase in mammalian cells. By targeting EGFP-tagged Na,K-ATPase 1 and {beta}1 subunits using anti-GFP nanobodies, we obtained high-density 3D localization maps of the protein in the plasma membrane. To evaluate the point patterns, we developed a computational data-driven spatial point assignment approach that segments apical and basal localizations, mitigating clustering artifacts produced by imaging two membranes in close proximity. Furthermore, we used a spatial statistical approach analyzing sequential nearest-neighbour distances to elucidate supramolecular arrangement information. Our data reveal a preferential nearest-neighbour distance of approximately 7 nm, providing direct visual confirmation of Na,K-ATPase dimerization. Additionally, we identified higher-order nanoclusters composed of up to 21 proteins. These findings provide definitive structural evidence of the dimeric configuration of Na,K-ATPase, establishing a foundation for future research on the functional and regulatory implications of Na,K-ATPase clustering.

Single-particle tracking (SPT) over time enables direct observation of molecular transport and interactions in living cells. Fluorescence-based SPT has provided insights into intracellular processes such as endocytosis, receptor signaling, and drug delivery. Extending the observation window to several hours and beyond is critical for capturing slow intracellular dynamics, including the full course of endosomal trafficking, the long-term accumulation of particles within subcellular compartments, and transitions between transport modes that occur on hour-scale timescales. However, long-term intracellular SPT under visible-wavelength excitation remains challenging because fluorescence probes generally suffer from photobleaching and phototoxicity. While near-infrared (NIR) excitation can simultaneously mitigate these issues, generally weak emission of NIR-emitting dyes has hindered its wide application in long-term SPT. Here, we demonstrate long-term NIR SPT using atomically precise gold quantum needles, Au42(PET)32 (PET = 2-phenylethanethiolate). Continuous tracking of intracellular particles in living HEK293 cells was achieved for up to 12 h. Trajectory analysis revealed temporal transitions between directional and diffusive transport, as well as the accumulation of multiple particles within localized intracellular domains over several-hour timescales. The high photostability of Au42, combined with low phototoxicity of NIR excitation, enables visualization of intracellular transport dynamics over timescales difficult to access using conventional visible fluorescent probes. These results establish Au42-based NIR imaging as a platform for long-term, low-phototoxicity intracellular SPT and provide a framework for investigating slow intracellular dynamics in living systems.

DNA-programmed assembly of plasmonic nanostructures provides a powerful route to couple molecular recognition with optical signal generation. Here, we report the sequence-specific assembly of DNA-functionalized gold nanorods using a sesame allergen-derived DNA biomarker as a molecular bridge. Target-induced assembly produces concentration-dependent assembly growth, plasmon coupling, and distinct assembly kinetics that are readily monitored by absorption spectroscopy, enabling label-free detection of the target DNA in the nanomolar concentration range. The assembled nanorods further produce strong surface-enhanced Raman scattering (SERS) signals arising from plasmonic coupling within the assemblies, extending detection to the picomolar regime without the use of Raman reporters. Quantitative analysis reveals that both the extent and rate of assembly formation are governed by target DNA concentration. These results establish a direct relationship between molecular recognition, assembly growth, plasmonic coupling, and spectroscopic response, highlighting DNA-programmed gold nanorod assembly as a versatile platform for investigating hybridization-driven plasmonic self-assembly and nucleic acid detection. Table of Content O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/732610v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@6a8f42org.highwire.dtl.DTLVardef@1e36b9corg.highwire.dtl.DTLVardef@1ade546org.highwire.dtl.DTLVardef@1a787bd_HPS_FORMAT_FIGEXP M_FIG C_FIG

Localized measurements of electric fields offer a promising route to expand the information content of nanopore-based single-molecule sensing beyond conventional ionic-current blockade. Here, using all-atom molecular dynamics simulations with virtual electric-field probes placed around a graphene nanopore, we show that the local electric-field captures the presence, and distribution of charged amino acids as the peptides translocate through the pore. These field signatures create reproducible peptide-specific fingerprints across independent translocation events and enable substantially improved discrimination between peptides compared with ionic-current traces obtained under the same simulation conditions. Our results suggest that localized nanopore electrometry can provide a complementary, information-rich readout of peptide charge order that is largely inaccessible to conventional current blockade-based measurement. This study establishes a simulation-guided framework for integrating nanoscale electrometry with nanopore platforms for future peptide and protein analysis.

A comprehensive understanding of the mechanisms underlying biological systems requires correlative analysis of multiple complementary molecular properties through multidimensional measurements. High-speed atomic force microscopy (HS-AFM) is a powerful tool for elucidating biomolecular structural dynamics at the single-molecule level with high spatiotemporal resolution. However, structural information alone is often insufficient for fully understanding the biological function mechanisms. Here, we report high-speed atomic force-Raman microscopy (HS-AFRM), which enables multimodal measurements combining video-rate structural imaging with chemical-bond analysis. Raman spectroscopy is a powerful, non-invasive technique that probes molecular vibrations to provide chemical information. We achieved several key technical developments that facilitated the seamless integration of HS-AFM and micro-Raman spectroscopy, allowing reliable correlative measurements of structural and chemical information. We validated the versatility of the developed system using representative samples, including two-dimensional materials and a protein. Furthermore, we demonstrate probing of changes in the surrounding environment, which are inaccessible by HS-AFM alone. Multimodal measurements incorporating fluorescence spectroscopy were also demonstrated as an additional practical extension. This multimodal approach substantially enhances the analytical capability of HS-AFM, providing a powerful platform for revealing correlated structural and chemical properties across diverse research fields.

PIEZO channels are mechanosensitive membrane proteins whose activation is governed by the surrounding lipid environment. However, the direct mechanistic contribution of native membrane composition to the molecular interactions remains unclear. In this study, a systematic comparison is made between PIEZO1 reconstituted in detergent micelles and in cell membrane-derived nanodiscs, which preserve the native lipid composition. Initial characterization employing a combination of atomic force microscopy and coarse-grained molecular dynamics simulations unveils distinct physical signatures of PIEZO1 in these two environments. Single-molecule force spectroscopy measurements demonstrate that interaction between the extracellular domain of PIEZO1 and a specific antibody exhibits unique mechanical responses strongly influenced by the surrounding membrane. In nanodiscs, PIEZO1 exhibits reversible, elastic-like behavior with preserved structural integrity and consistent adhesion forces even when modulated by Yoda1 (agonist) and Dooku1 (antagonist). Conversely, micelles induce a plastic response with altered mechanosensitivity and functional stability. Based on these findings, we propose a possible membrane-mediated force transmission pathway and quantify a simplified interaction energy landscape. Collectively, our findings offer the initial direct evidence of how the native lipid environment mechanistically governs PIEZO1 interactions, establishing native membranes as critical determinants for mechanotransduction.

The molecular programmability of nucleic acids has facilitated the development of architected DNA/RNA nanostructures and their applications in novel materials and technologies. We report how different types of DNA and RNA nanoaggregates, bundling digital information encoded into oligo libraries, can be formed by manipulating the ionic strength of the solution. As DNA or RNA suspensions are immersed in solutions of increasing salt concentrations, we observe the onset of aggregation. Further increase in ionic strength leads to the formation of stable, reproducible, and well-defined aggregates. We show that these nanoaggregates are kinetically trapped at room temperature, stably partition DNA libraries that encode image files, and support file-specific random access by bundling DNA libraries with unique address oligos. The nanoaggregate files can be disrupted and reformed into scrambled bundles using simple external fluid shear or temperature annealing, rapidly obfuscating the data. We term these nanoaggregates nucleic acid PACKeTs: Partitioned Aggregates of Colloidal DNA/RNA through Kinetic Trapping. Overall, the results demonstrate how gaining fundamental insights into ionic colloidal aggregation enables new forms of manipulation of DNA and RNA libraries. This understanding could lead to novel functionalities including kinetically trapped data partitioning, random access, and data encryption or obfuscation.

Precise drug delivery within anatomically complex tissues demands systems capable of both active navigation and deep tissue access, properties that have remained difficult to reconcile in existing nanocarriers and microrobots. Here we introduce Dynabots, a dynamic microrobotic assembly constructed from multifunctional nanoparticles covalently linked by thermally cleavable molecular connectors. This nanoparticle-rich architecture enables the integration of magnetic, imaging, and therapeutic components while preserving a high content of functional material. Collective assembly imparts enhanced magnetic responsiveness and maneuverability, enabling controlled navigation through tortuous biological environments. Upon exposure to mild thermal stimuli, the assemblies undergo programmed disassembly, releasing individual nanoparticles that can diffuse through tissue for localized therapeutic action. We establish the programmable transitions, biocompatibility, and therapeutic efficacy of this process across in vitro and in vivo models, including real-time fluoroscopic guidance within anatomically realistic phantoms and live rodent and porcine systems. By integrating magnetic control, reconfigurable architecture, and stimulus-triggered disassembly, Dynabots unite navigational precision with tissue permeability, providing a versatile platform for adaptive and deep-tissue drug delivery.

DNA is highly programmable and efficient for encoding information. In this work, we use the paranemic crossover (PX) DNA structures for a binary-encoded system. As substrates for data storage, we designed a combination of PX and anti-PX structures where the four strands of the PX motif are complementary to those in the anti-PX motif. To write data, we programmed encoding elements in each of the four strands of the PX and anti-PX motifs. The encoded data remains encrypted until the samples are processed at a specific temperature, when the PX and anti-PX motifs reassociate to four distinct duplexes, defined by the encoding elements and retrieved using an electrophoretic readout. We show that the encoded information is stable for several days when stored at 20 {degrees}C, 37 {degrees}C or outdoors, with the encrypted structures showing higher nuclease resistance compared to the decrypted structures. Using this strategy, we demonstrate hexadecimal encoding using a combination of 4 bits, encrypting specific words and color codes. We envision such systems could find use barcoding, secure messaging and authentication.

Scanning ion conductance microscopy (SICM) provides gentle, non-contact cell surface imaging, but it has not been used to investigate intracellular structures because the plasma membrane restricts nanopipette access. Here, we combined SICM with microsonication-based cell de-roofing to expose intracellular actin stress fibers (SFs) in U2OS cells for nanotopographical and -mechanical characterization. Importantly, the de-roofing conditions preserved actomyosin contractility, allowing analysis of SF structural and biomechanical changes during ATP-induced contraction. Resting SFs displayed an average height of 203{+/-}38 nm and width of 357{+/-}73 nm, and a complex surface architecture characterized by regularly spaced long-range height modulations (~500 nm periodicity; Wq ~25 nm) and smaller irregular corrugations (Ra ~19.2 nm). ATP stimulation reduced SF height and width by ~39% and ~15%, respectively, while largely preserving surface corrugation patterns. During contraction, some SFs separated into two longitudinal strands. High-resolution SICM imaging also revealed filamentous crosslinks mechanically coupling neighboring SFs, and nanomechanical measurements demonstrated local stiffening during contraction. These findings provide new insight into the structural and mechanical regulation of SF contraction and highlight the potential of SICM combined with cell de-roofing as a powerful platform for studying dynamic intracellular processes at nanometer resolution.

The cytoskeleton determines cell shape, mechanical properties, and motility by interconnected networks of protein filaments - actin filaments, microtubules and intermediate filaments. Their collective function relies on crosstalk between these filament systems, yet the physical basis of interactions between the filaments remains insufficiently understood. Actin and vimentin filaments and networks frequently co-localize within cells and jointly regulate contractility, force transmission and mechanical resilience, indicating functional cooperation. However, it remains unclear whether these interactions arise from direct filament-filament interactions or are mediated exclusively by accessory crosslinking proteins. Studies of reconstituted composite networks probing direct interactions by rheology have yielded inconsistent results. Here, we show that single actin filaments and vimentin intermediate filaments do indeed interact directly, forming force-bearing contacts in the absence of crosslinking proteins, with interaction strengths comparable to other previously reported cytoskeletal filament pairs. Using quadruple optical tweezers combined with microfluidics and confocal microscopy, we systematically probe these interactions under controlled conditions across a range of ionic environments. We find that, in contrast to other filament pairs, variations in ionic strength do not appreciably affect the interaction breaking forces between actin and vimentin filaments. However, the interaction geometry determines the achievable interaction strengths, because the limited stretchability of the actin filaments sets an upper bound to the measurable force range. This limit also imposes a restriction on direct quantification of interaction parameters, which we circumvent by a Bayesian unmasking strategy that allows us to infer bond parameters despite the breaking of actin filaments. Furthermore, actin bundling enhances the stability against breaking, enabling the detection of higher interaction forces. These findings demonstrate that actin and vimentin form a mechanically interacting system through direct filament bonds, and our work establishes a minimal, protein-linker-independent physical basis for actin-vimentin crosstalk and quantifies the interaction forces between the two filament types.

Biomolecular condensates are important regulators of cellular compartmentalization and biochemical processes. Understanding their material properties is critical to elucidate how they control molecular organization and dynamics within cells. However, quantitatively probing these properties remains challenging due to the wide range of length scales, concentrations, and timescales over which condensates operate, as well as the limited force ranges accessible to current nanoscale mechanical mapping methods. We explored the use of a non-contact 3D imaging tool Scanning Ion Conductance Microscopy (SICM) for stiffness measurements of liquid-liquid phase-separated biomolecular condensates. We focus on the Dhh1 protein, which is a regulator of cytoplasmic processing bodies (PBs) membrane-less cytoplasmic condensates that control the storage and degradation of untranslated mRNA. In our study, we investigate the properties of mCherry2- or His-mCherry2- tagged full-length Dhh1 and N- or C-terminus tail-deletion constructs, as well as the catalytically inactive mutant DQAD, under different pH and incubation times. We mapped both spatial and temporal changes in the material properties of the condensates, highlighting the capabilities of the instrument. We found that the removal of either of the two tails led to an increase in condensate stiffness upon shifting the pH from a stress-associated cellular environment (pH 6.5) to physiological conditions (pH 7.5). Additionally, the choice of protein tags led to vastly different results depending on the pH where mCherry2-Dhh1 exhibited a stiffening going from pH 6.0 to 6.5 while the double-tagged His-mCherry2 did not. Our measurements are verified and corroborated by established techniques such as optical tweezer-based fusion assays and fluorescence recovery after photobleaching (FRAP). Furthermore, we were able to track the same biomolecular condensate sample for up to 20 days getting insights on the ageing and evolution of the condensates. Overall, our study demonstrates the applicability of SICM for direct measurement of the material properties of biomolecular condensate.

Governing thermal transport in engineered materials creates opportunities to redirect and recover the excess heat generated in electronic and energy-conversion devices. Materials that pair low cross-plane thermal conductivity with high in-plane thermal conductivity are particularly valuable because they confine heat and channel it away from sensitive regions, preventing localized device failure. Two-dimensional crystals are efficient building blocks for such anisotropic thermal conductors, but they are brittle, and the polymer composites used to toughen them usually forfeit much of the intrinsic anisotropy: in conventional percolation-based design, filler fraction is the only handle available, and it governs both in-plane and cross-plane conduction. Here we report a composite of Ti3C2Tx (MXene) nanosheets and squid ring teeth (SRT) inspired recombinant tandem-repeat (TR) proteins in which the protein serves as a molecular template and bridge, setting the spacing between nanosheets with angstrom-level precision through the number of tandem-repeat units and independently of the filler fraction. This structural handle provides a second, independent design parameter. At a fixed MXene loading, the number of repeats tunes the cross-plane conductivity (0.30 to 0.93 W/mK) and, with it, the thermal anisotropy ratio over a wide range (from about 70 down to 17), while the in-plane conductivity stays high (16 to 21 W/mK). We rationalize these trends with a Gaussian Network Model (GNM) of the protein embedded in a two-phase layered medium, which reproduces the measured directional conductivities from a single structural parameter and identifies the protein gallery as the cross-plane bottleneck. Extending the model to a mechanically loaded five-period stack, we find that the anisotropy is robust to reversible compression and twist, changing by only a few percent, so the number of tandem repeats, not the applied strain, is the dominant design handle. Because anisotropy is tuned structurally rather than volumetrically, these protein-MXene composites decouple thermal anisotropy from filler content, pointing toward flexible thermal materials that are not bound by the rules of mixture and percolation.

Living cells are highly dynamic and densely crowded environments in which organelles such as vesicles undergo continuous motion that is essential for cellular processes. Therefore, accurate tracking of individual organelles is crucial for understanding intercellular dynamics and functions. However, precise tracking of individual organelles in living cells remains challenging due to high organelle densities, frequent particle overlap, and the coexistence of stationary and motile organelles. In particular, stationary organelles can obscure the trajectories of moving organelles, leading to tracking errors and fragmented tracks. To overcome these challenges, we developed Multiple Particle Tracking via Velocity Filtering (MPT-vVF), an unbiased, semi-automated tracking framework that incorporates a mathematically derived velocity-filtering algorithm to selectively identify and track moving organelles with high accuracy in crowded intracellular environments. MPT-vVF integrates denoising, background subtraction, and a velocity-matching detection step that discriminates true particle motion from noise based on spatiotemporal continuity, followed by robust trajectory linking. We demonstrate that MPT-vVF can accurately resolve nanometer-scale displacements of immobilized beads, highlighting its high tracking precision. We also validate the robustness of MPT-vVF by quantifying the transport of brain-derived neurotrophic factor (BDNF)-mRFP-containing vesicles in living hippocampal neurons. Furthermore, MPT-vVF reveals that exposure to 50-nm nanoplastics impairs vesicular transport, reducing both travel length and speed of BDNF-containing vesicles in living neurons. These findings establish MPT-vVF as a powerful method for quantitative analysis of intracellular organelles in crowded living cells and suggest its broad application to biophysics, cell biology, and soft matter research.

The accurate quantification of biological nanoparticles, such as small extracellular vesicles (sEVs), is fundamentally hindered by a resolution-coincidence trade-off in digital assays. While physical confinement can isolate single particles, conventional optical readouts remain diffraction-limited, causing multi-particle occupancy to be miscounted as single events and thereby restricting the analytical dynamic range. Here, we report a nanoplasmonic platform that overcomes this limit by introducing a geometry-defined interface that uniquely unifies nanoscale compartmentalisation and near-field-assisted super-resolution imaging. Utilising a gold plasmonic nanohole array, the strict geometric periodicity of the lattice simultaneously serves as a template for single-vesicle confinement and a deterministic grid that generates an array of localised surface plasmon resonance near-field hotspots. This position-deterministic illumination pattern imposes known geometric priors on the excitation field, shifting high-spatial-frequency information into the detectable bandwidth to achieve sub-100 nm lateral resolution. This dual-purpose geometric determinism enables high-fidelity digital readout of individual vesicles with significantly fewer sub-images than stochastic, speckle-based metasurface structured illumination microscopy approaches. The assay achieves an analytical limit of detection of 143 sEVs/{micro}L, matching the performance of state-of-the-art single-EV counting technologies. It successfully differentiates distinct sEV subpopulations based on surface biomarker expression, establishing a clear pathway for future clinical liquid biopsy applications. By replacing stochastic loading and illumination with geometric design, this work establishes a robust framework for precise vesicle interrogation with broad implications for emerging translational applications and fundamental biology.

We report a generalizable method for single-molecule localization super-resolution microscopy in living cells. Live-cell protein-based PAINT (points accumulation for imaging in nanoscale topography) is achieved by pairing exceptionally fluorogenic bis-trifluoromethyl rhodamine (BF) dyes with reversible HaloTag ligands. This far-red small molecule update to protein-based PAINT is readily incorporated into existing super-resolution microscopy workflows: pairing with photoactivatable fluorescent proteins further enables simultaneous two-color live-cell super-resolution microscopy and single-molecule diffusivity mapping (SMdM).

DNA-based technologies rely on short, transient hybridization events, but selecting sequences with desired kinetic properties remains largely empirical because hybridization kinetics are difficult to predict from sequence and slow to measure one sequence at a time. Here, we introduce SPARXS-Hyb, an implementation of SPARXS (Single-molecule Parallel Analysis for Rapid eXploration of Sequence space) for multiplexed sequence-resolved screening of DNA hybridization. Using a surface-immobilized docking-strand library and a quencher-labelled imager-strand library, we screened 128 different DNA sequences in a single kinetic measurement, exposing all sequences to identical experimental conditions. This multiplexed approach removes a major confounding factor of serial measurements, allowing sequence-dependent differences to be compared directly. The resulting dataset reveals sequence-dependent transient binding behaviours and enabled us to identify a sequence with which an order-of-magnitude higher sampling rate can be achieved in DNA-PAINT (DNA points accumulation for imaging in nanoscale topography), a super-resolution microscopy technique based on DNA hybridization. By enabling multiplexed screening across a sequence library, SPARXS-Hyb provides a route to kinetics-guided sequence selection for programmable transient interactions in DNA nanotechnology.

Adhesion of cells is the key factor determining functioning of multicellular organisms. Viscoelastic properties of cells can be studied by multiple methods. However, attractiveness of cells or extracellular matrix without the elastic component (dispersive adhesion) is not accessible. We present an extension of force spectrometry technology: the Multivalent Adhesive Probe Atomic Force Microscopy (MAPA) that delivers dispersive adhesion maps of live cells and biosurfaces, and identifies differences unresolved by viscoelastic probing.

Recent work has shown that genetically engineered proteins can serve as quantum bits in living systems. These quantum bits arise from the photochemistry of protein-bound flavins: blue-light excitation drives electron transfer to form a spin-correlated radical pair whose coherent singlet-triplet interconversion makes the protein's fluorescence sensitive to weak magnetic fields. Because this radical-pair reaction depends on the redox state of the flavin, itself a central electron carrier in cellular metabolism, the magneto-fluorescence of a biological qubit is intrinsically coupled to the biochemistry around it. This suggests a powerful application of fundamental significance in biology, until now an unsolved problem in the field of quantum sensing. Here we show a new class of quantum sensor, mtMagLOV2, that interfaces directly to a defining feature of life itself: the bioenergetic state of the cell. We genetically engineer flavin mononucleotide (FMN)-containing, magnetic-field-sensitive fluorescent proteins (biological qubits) to be expressed and translocated into the key bioenergetic machinery of the cell: the mitochondrial matrix. Using confocal and super-resolution microscopy, mtMagLOV2 localizes to the mitochondrial cristae, home of the electron transport chain complexes I-V and ATP synthase, the site of oxidative phosphorylation (OXPHOS). By pharmacological manipulation of OXPHOS, we show that the sensor's magneto-fluorescence tracks the redox (oxidation, reduction) state of the mitochondrial flavins, providing a quantum readout of redox status. The response differs between cancer cells (which rely heavily on glycolysis) and cardiomyocytes (which rely predominantly on OXPHOS), demonstrating quantum bioenergetic profiling. Together, these results establish biological qubits as quantum sensors capable of probing mitochondrial bioenergetics, opening a quantum window into the energetic machinery of living cells. More broadly, we anticipate that coupling quantum redox sensitivity to the specific biochemical targets will extend the reach of quantum technologies across the life sciences.