Soft Matter

Flow and extensional deformation of mucin networks are fundamental in mucus biophysics, governing how mucus functions as a protective and lubricating, and transport-facilitating layer. While the shear and oscillatory rheology of mucin solutions have been characterized in considerable detail, their behavior under extensional deformation remains comparatively understudied. Here, we report a concentration-dependent transition in extensional flow response of mucin solutions using a bespoke dripping-onto-substrate extensional rheometer. We show that mucin solutions at the lower concentrations undergo linear filament thinning, whereas semidilute mucin solutions form highly extensible filaments, with radius decaying exponentially in time, consistent with the elastocapillary thinning observed in solutions of high molecular weight synthetic polymers. Remarkably, at higher mucin concentrations inter-chain mucin associations produce a sudden reduction in the apparent elastocapillary relaxation time. We demonstrate how increasing macromolecular concentration redistributes the balance between viscous and elastic stresses during capillary thinning in a biopolymer network and reveal a concentration-driven reduction in mucin filament extensibility. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/725541v2_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@1f593acorg.highwire.dtl.DTLVardef@1b23686org.highwire.dtl.DTLVardef@119add3org.highwire.dtl.DTLVardef@e31908_HPS_FORMAT_FIGEXP M_FIG C_FIG

In mammalian cells, lipid monolayers support the integrity of lipid droplets (LDs), organelles that function as storage for neutral lipids. Liver-targeting illnesses such as liver cancer interrupt normal LD metabolism and prompt changes in the chemical content of these organelles, which can have effects on structural and organizational behavior of the lipids. In LDs, liver cancer induces concentric crystalline phases of cholesteryl esters (CEs) and triglycerides near the NL-monolayer interface, which become more pronounced as CE concentration increases. Yet, there is little known about how this phenomenon may link to persistence of undigested LDs in liver cancer patients. To shed light on this, all-atom molecular dynamics simulations were used to model LD micropipette aspiration experiments and gain insight into the effect of CE concentration on partitioning, structural, and mechanical properties of LDs. We successfully model micropipette aspiration by application of constant surface tension laterally, which stretches lipid bilayers and monolayers as the magnitude increased. The results show increased phospholipid packing due to insertion of CE fatty tails into the monolayer. Increasing CE concentration induces a non-linear change in surface packing defects on the LDs, notable rigidification, and stiffness. Taken together, these insights improve our understanding of the physical properties at the LD monolayer-core interface during liver cancer progression.

Significant cellular processes, including protein sorting, signal transduction, and pathogen entry, amongst others, are associated with membrane microdomains, also known as lipid rafts. Lipid rafts, due to their unique biophysical properties compared to their surrounding environment, which stem from their distinct lipid and protein profiles, have garnered interest in methods and techniques that tune their coexisting liquid-ordered/liquid-disordered state, aiming to disrupt or destabilize them. Since cholesterol stabilizes the membrane domain, cholesterol-depleting compounds like cyclodextrin can be used to destabilize and disrupt the membrane rafts. Overall, given the membrane rafts importance in biological processes, it is crucial to understand the biophysical factors that influence its stability. In this study, we present a new method for disrupting and dissolving lipid rafts in a model system of phase-separated supported lipid bilayer (SLB) patches composed of DOPC, DPPC, and cholesterol. Using fluorescence microscopy to monitor the liquid ordered (Lo) and liquid disordered (Ld) phases of the SLB patches, we observed that adding DOPC liposomes causes a transformation of the co-existing Ld and Lo phases into a single-phase bilayer. On the other hand, adding liposomes that match the lipid content of the phase-separated SLB patch increase the areas of the existing Ld and Lo phases. This work also offers a new method for redistributing raft-localized molecules, confirmed by tracking the redistribution of cholera toxin bound to GM1 after domain dissolution with DOPC liposomes. The work describes an alternative method for dynamically altering membrane composition and dissolving domains via liposome addition, rather than lipid depletion or exchange.

Although organelles are often studied one at a time, whole-cell imaging studies show that organelles take up a large part of the cell volume such that they are crowded together. Here we use whole cell soft X-ray tomography imaging to investigate how such crowding affects organelle size scaling, position, and shape, focusing on the nucleus and vacuole of budding yeast. We find that as the vacuole becomes larger, the nucleus loses its normal scaling relation with respect to cell volume, becomes displaced from its normal position near the cell center, and becomes progressively deformed from a sphere into a pancake shape. Using a whole-cell integrated modeling framework, we find that these changes are statistically correlated and give rise to distinct modes in cell organization space. Using a simplified mechanical model for two initially spherical compartments contained inside a confined intracellular space, we are able to recapitulate the effects seen in the experimental data, indicating that these observations are consistent with a purely mechanical interaction. Taken together, our work indicates that, in addition to the well-known protein-based organelle-organelle interactions, physical steric packing of organelles inside a limited cellular volume also plays a large role in the inter-organelle relationships and the overall geometry of the cell.

Sustainable, biodegradable elastomers are needed to replace fossil-based alternatives and reduce the environmental impact of traditional vibration damping materials. We investigate agarose-based hydrogels as eco-friendly vibration absorbers, examining the combined effects of polymer concentration (1-7 wt%), relative humidity (55-98%), and mechanical pre-stress on their dynamic mechanical properties. Frequency-dependent viscoelastic and vibration transmissibility tests, supported by Gaussian Process Regression (GPR), reveal that increasing agarose concentration enhances the storage modulus (E') by over an order of magnitude, reaching[~] 5 MPa depending on humidity and applied prestress. Remarkably, the damping efficiency--characterised by the loss factor (tan(d))--exhibits a highly non-monotonic trend. Maximum energy dissipation is observed at intermediate network densities, with tan(d) up to 0.21 and a loss modulus of[~] 515 kPa at 5 w% and 75% relative humidity, comparable to synthetic elastomers. GPR analysis shows that prestress controls nonlinear stiffening and transmissibility resonance behavior, while shifting peak damping from 5 wt% to 1 wt% agarose as prestress increases. These findings underscore the mechanical tunability and sustainability of agarose hydrogels, providing potential design guidance for biodegradable vibration mitigation materials.

Mechanical properties of epithelial tissues play essential roles in morphogenesis and physiological function. In this study, we analytically derived the in-plane bulk modulus, shear modulus, and Poissons ratio of a three-dimensional cell vertex model of epithelial monolayers. We showed that the model can robustly reproduce a near-zero in-plane Poissons ratio, a mechanical feature reported in cultured epithelial tissues. Numerical simulations further confirmed that the theoretically predicted Poissons ratio accurately describes the response of the model under finite, biologically relevant strains. In addition, the model exhibits not only morphological bistability between squamous-like and columnar-like states, but also mechanical bistability characterized by distinct elastic responses. Together, these results provide a minimal three-dimensional framework that links cell-scale mechanical interactions and epithelial morphology to tissue-scale elastic properties.

Detergent-free extraction of membrane proteins using polymers directly into nanodiscs from the cell membrane has been used widely in recent years. Since the first use of poly(styrene-co-maleic acid) (SMA), numerous related polymers have been developed that differ in chemical architecture and nanodisc characteristics, each capable of influencing the structural and functional properties of the encapsulated membrane protein and its surrounding lipids. Identifying an optimal solubilising polymer, therefore, requires consideration not only of extraction efficiency but also compatibility with downstream applications and analyses. Polymer series in which a single parameter is systematically varied provide a valuable, nuanced tool for optimising nanodisc utility in downstream applications. This study utilises a chemically defined series of poly(styrene-co-maleic acid-co-(N-benzyl)maleimide) (BzAM) terpolymers that exhibit a stepwise, systematic increase in hydrophobicity. Using the human calcitonin gene-related peptide (CGRP) receptor as an exemplar class B1 G-protein-coupled receptor (GPCR), the ability of each BzAM terpolymer to solubilise the receptor from mammalian cell membranes was assessed. All members of the series successfully solubilised CGRP receptor, with solubilisation efficiency correlating positively with increasing hydrophobicity. Importantly, the receptor retained its characteristic high-affinity ligand-binding capability when encapsulated within the BzAM nanodisc, demonstrating that functional integrity is preserved following BzAM-mediated extraction and purification. These findings establish the BzAM terpolymer series as a systematic, tuneable, well-defined tool for the detergent-free solubilisation and functional investigation of GPCRs, and other membrane proteins, in near-native lipid environments. HIGHLIGHTSO_LIStepwise-tuned poly(styrene-co-maleic acid-co-(N-benzyl)maleimide) (BzAM) terpolymers provide a chemically defined, hydrophobicity-controlled platform for detergent-free membrane protein extraction. C_LIO_LIAll BzAM variants effectively solubilise the human calcitonin gene-related peptide (CGRP) receptor, with extraction efficiency increasing in line with terpolymer hydrophobicity. C_LIO_LICGRP receptor maintains high-affinity ligand binding in BzAM nanodiscs, demonstrating preservation of ligand-binding function after solubilisation. C_LIO_LIThe BzAM series provides a novel platform for studying G-protein-coupled receptors and other membrane proteins in near-native lipid environments, with the potential to deliver mechanistic insights and support future drug-discovery efforts. C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/726474v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@1cb167corg.highwire.dtl.DTLVardef@313e60org.highwire.dtl.DTLVardef@f64a2borg.highwire.dtl.DTLVardef@17f6629_HPS_FORMAT_FIGEXP M_FIG C_FIG

Cytoplasmic mechanical properties are often treated as constant background parameters, yet whether they change systematically during development remains unclear. Here, we directly measured cytoplasmic mechanics during early embryogenesis of Caenorhabditis elegans by establishing active microrheology using micrometer-sized magnetic droplets. Active microrheology revealed a progressive decrease in creep compliance from the 1-cell to the 8-cell stage, indicating a progressive stiffening of the local cytoplasmic environment during development. This decrease persisted even when cytokinesis was inhibited, demonstrating that it cannot be explained solely by geometric changes associated with cell division. Passive microrheology using 40-nm fluorescent beads showed a consistent decrease in probe mobility over development. Together, these results demonstrate that cytoplasmic mechanical properties undergo a gradual, developmentally programmed change during embryogenesis that cannot be explained by cell division-associated geometry alone.

Hemodynamic forces play a key role in early cardiac morphogenesis, yet many computational studies assume Newtonian blood behavior. Here, we evaluate the impact of nonNewtonian shearthinning rheology on flow patterns, pressure distributions, and wall shear stress (WSS) during cardiac looping using idealized threedimensional models of the embryonic heart tube. Five geometries representing progressive looping stages, from a linear tube to an Sshaped configuration with ventricular ballooning, were analyzed under pulsatile flow using both Newtonian and powerlaw viscosity models. Across all stages, Reynolds numbers (Re {approx} 1-7) and Womersley numbers (Wo {approx} 0.3) indicated laminar, quasisteady flow consistent with embryonic conditions. Incorporating shearthinning rheology produced substantial deviations from Newtonian predictions, with peak systolic WSS differing by up to [~]40% and pressure drops by up to [~]20%. These effects were most pronounced in regions of increased curvature and geometric complexity. These findings demonstrate that nonNewtonian rheology significantly influences predicted hemodynamic environments during cardiac looping and should be incorporated into computational models aimed at understanding mechanobiological regulation of early heart development.

Embryonically, the vertebrate brain begins as an approximately uniform, fluid-filled epithelial tube that undergoes rapid volumetric expansion and regionalization to form the morphologically distinct primary brain vesicles. Hydrostatic pressure from fluid secretion into the inner lumen generates tension in the neural tube that has been implicated as a potential driver of cell proliferation during these early stages of brain development. However, a quantitatively rigorous view of 3D morphology and cellular proliferation has remained elusive. Here, we provide a standardized mapping for the mechanical and biological landscape of the developing neuroepithelium along anatomical axes. Using this 3D morphometric framework in chicken embryos, we show that localized curvature characterizes compartmental boundaries. While rapid inflation would typically be expected to stretch and thin the epithelium, we find the opposite: global expansion is coupled with significant tissue thickening, identifying the early brain as an active shell. Moreover, spatial patterns of thickness remain invariant to local curvature. Our results demonstrate a decoupling of geometry and growth, showing that spatially stable distributions of tissue thickness and mitotic activity are maintained throughout massive volumetric expansion, independent of the dramatic geometric reorganization driven by luminal pressure. We conclude that, while tension in the neuroepithelium may contribute to proliferative growth at some level, biological pre-pattern likely plays a driving role in the regionalized expansion of the early embryonic brain. Why it mattersThe embryonic brain begins as a simple fluid-filled tube that undergoes rapid and heterogeneous expansion to set up the basic organizational plan of the adult brain. Errors in this process are linked to severe neurological and congenital disorders. This work investigates the biophysical basis of expansion and regionalization of the early brain, a complex three-dimensional process driven by inflation from internal fluid pressure together with active cell behaviors that ultimately produce regionally distinct growth and curvature profiles amid a complex mechanical landscape. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/726048v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@17c442forg.highwire.dtl.DTLVardef@1609374org.highwire.dtl.DTLVardef@170c00corg.highwire.dtl.DTLVardef@15080ad_HPS_FORMAT_FIGEXP M_FIG C_FIG

Cell migration is fundamental to various biological processes, including morphogenesis, wound healing, and cancer metastasis. Durotaxis--directed migration of cells in response to spatial variations in stiffness--has been extensively studied using engineered substrates with prescribed stiffness. However, recent work has increasingly shifted toward understanding cell migration in fibrous matrices that can be actively remodeled by the actomyosin contractility, as commonly observed in tumor and epithelial cells. Despite these advances, a theoretical framework explaining how cells structurally remodel their surrounding matrix to promote their own durotaxis, and which cellular forces govern this behavior, remains elusive. To address this gap, we developed a biomechanical model in which polarized cells contract and migrate over a fibrous matrix. Using this model, we first confirmed that cells on an externally strained matrix preferentially migrate along the direction of applied strain. Then, we investigated how cells autonomously remodel the matrix to create stiffness patterns favorable for durotaxis. In the presence of intercellular adhesion, cells acted collectively to stiffen the matrix, after which a small subset of cells escaped the main population and migrated outward. This behavior is reminiscent of intravasation during cancer metastasis, where cohesive cell clusters generate local matrix remodeling that facilitates the departure of more motile subpopulations. These results illustrate how matrix stiffening driven by cell cohesion and contractility regulates durotactic behavior and provide mechanistic insight into collective invasion processes relevant to cancer metastasis.

Understanding how biological shape and movement interact with surrounding fluids represents a fundamental challenge at the intersection of biology, physics, and engineering. Fish locomotion exemplifies this challenge: body morphology and swimming kinematics together determine the hydrodynamic forces and flow structures that enable efficient propulsion and maneuverability. Whereas biologists have long sought to connect morphological variation to swimming performance, traditional morphometric approaches provide limited insight into the fluid mechanical consequences of shape differences. Similarly, although computational fluid dynamics can reveal detailed flow physics, simulating hydrodynamics across diverse and dynamic morphologies remains prohibitively expensive for systematic investigation. To bridge this gap, we introduce a data-driven framework that connects fish body shape dynamics to hydro-dynamic performance through compact morphospace parameterization and reduced-order modeling. Using CFD simulations of 15 fish species from the Digital Life Project database (www.digitallife3d.org/3d-model), we generate hydrodynamic datasets capturing the shape-flow relationship. Principal Component Analysis (PCA) extracts four dominant shape parameters from dorsal body profiles, which are then integrated into an Inverse-Design with Dynamic Mode Decomposition (ID-DMD) framework to model the resulting fluid dynamics. The resulting modal analysis suggests that locomotion strategies emerge from specific shape-flow interactions. We further demonstrate the frameworks utility through single- and multi-objective shape optimization, showing how it enables efficient exploration of the morphology-hydrodynamics relationship. This approach offers a novel analysis and design tool for understanding how biological form and motion interact with fluid mechanics, with applications ranging from bio-inspired vehicle development to evolutionary biomechanics.

Membrane models of scaffolded discoidal lipid bilayers called nanodiscs have proven to be a valuable tool for the study of membrane proteins in a native environment. DNA-scaffolded membrane model has emerged as an alternative tool for membrane protein studies. Taking advantage of the designability of DNA nanostructure, we created a double-decker double-stranded DNA ring (DDring) to self-assemble DNA-based nanodiscs (DNA-ND). The DDring is 17 nm wide and 4 nm high, and equipped with 28 alkyl chains on the inside that can interact with each hydrophobic leaflet of the lipid bilayer. We further demonstrate the functionality of DNA-ND membrane model with the assembly of membrane proteins. DDrings are suited to neutral or cationic charged phospholipids and detergents. This study provides more insights into the potential use of DNA- assisted nanodiscs for membrane protein characterization.

Hydrogels are the preferred materials for applications mimicking soft tissues due to their high water content and tunable mechanical properties. The state of the water in these hydrated networks governs their response to mechanical loading through coupled interstitial flow and large deformations of the solid network. Reliable experimental methods for quantifying the fraction of mobile fluid during mechanical deformation remain limited. Within the theoretical framework of mixture theory, we describe hydrogels as hydrated biphasic media consisting of a deformable incompressible solid matrix and a mobile fluid phase. We developed a mechanical testing protocol that enables the experimental separation of solid and fluid contributions under loading. The method is demonstrated using biocompatible and highly versatile hydrogel phantoms of varying compositions. Controlled, incremental drained confined compression of the hydrogel samples results in free-water fractions of approximately 40%, 60%, and 77%, reflecting the systematic influence of the polymer content on the porosity and fluid mobility. Comparison with cryo-SEM-derived surface porosity reveals statistically significant differences and highlights the scale-dependent sensitivity of surface measurements compared to bulk measurements. This study introduces a new mechanical method for quantifying the free-water fraction in macroporous, ultrasoft, highly hydrated biomaterials. Furthermore, the multi-step protocols enable the separation of dissipative, fluid-related relaxation from the equilibrium response of the solid skeleton, allowing direct calibration of constitutive models for macroporous soft solids. The proposed method provides a reliable basis for the development and optimization of hydrogels for applications where fluid transport is critical, such as neural interfaces, bioelectronic platforms, and tissue-engineered constructs.

TRPA1 is a polymodal ion channel receptor known for its role in nociception. TRPA1 can be activated by local mechanical perturbations in the surrounding plasma membrane (PM) by molecules that insert in the lipid bilayer. Here, we tested whether TRPA1 function can be modulated by lipid nanoparticles (LNPs) while interacting with the target cell plasma membrane. We found that LNP induce irregular Ca2+ transients in heterologous and native TRPA1-expressing cells, which may reflect stochastic LNP-PM interactions. By using different cell types and applying selective and non-selective TRPA1 inhibitors, we revealed that the cytosolic [Ca2+] is elevated transients arise as a result through multiple mechanisms: TRPA1-dependent Ca2+ influx, TRPA1-independent Ca2+ influx, and Ca2+ mobilization from the endoplasmic reticulum. Our results describe a novel, non-canonical TRPA1 activation mechanism by LNPs, that may be relevant in the context of the development of cancer and nasal vaccines.

Cell migration plays a central role in numerous physiological and pathological processes and emerges from the coordinated interplay between intracellular force generation, adhesion dynamics, and mechanical interactions with the environment. A minimal, mechanistically grounded understanding of these processes is required to disentangle the respective contributions of cell-intrinsic and environmental cues. Here, a two-dimensional in silico cell motility model is introduced to describe mesenchymal migration driven by intracellular traction forces generated within actin-rich protrusions anchored to a substrate. The model explicitly accounts for adhesion nucleation, maturation, force buildup and rupture, and relies on a small set of physically interpretable parameters. A systematic mechanical analysis identifies parameter regimes that permit effective cell translocation and delineates conditions leading to stalled or mobile cells. Within motile regimes, the model reproduces a broad spectrum of cell morphologies and migratory behaviours. In particular, cell trajectories exhibit the statistical features of a persistent random walk, with a crossover from ballistic to diffusive motion that arises solely from adhesion dynamics and force balance, without imposing polarization or directional bias. Cell morphology is shown to strongly regulate migration speed, persistence, and pausing behaviour. Altogether, this model provides a minimal reference framework for cell migration on non-deformable substrates and establishes a baseline for future studies of mechanically driven guidance. By construction, it is well suited for extension to deformable fibrous substrates, where cell-induced matrix remodeling and stiffness feedback are expected to bias migration and regulate cell encounters relevant to tissue morphogenesis and anastomosis.

Liposomes are self-assembled lipid vesicles capable of encapsulating both hydrophilic and hydrophobic therapeutics, making them versatile platforms in drug delivery and biomedical technology. In this study, the limitations of the classical thin-film hydration method were critically evaluated, and a sustainable, systematically optimized strategy was established for generating defined liposomal lamellar phases. Hydration conditions were optimized, and 4 mL of buffer per 10 mg of lipid was determined to be optimal for effective rehydration and improved statistical reliability of vesicle measurements. A refined probe-sonication protocol (20% amplitude, 5 s ON/55 s OFF pulse) enabled controlled transformation of multivesicular vesicles into stable multilamellar and unilamellar vesicles at net ON-times of 90 s and 185 s, respectively, without overheating or contamination. In addition, a Python-based machine-learning tool was developed for vesicle size characterization. Collectively, these optimizations provided a reproducible and sustainable framework for preparing liposomes across different lamellar phases.

Frustrated phagocytosis occurs when phagocytes fail to fully engulf large targets, yet the geometric origins of this physical limit remain poorly defined. Here we present a geometric model that identifies the cell nucleus as an intracellular constraint on engulfment. Extending membrane-limited frameworks, we distinguish an intrinsic phagocytic capacity set by membrane availability from an apparent capacity reduced by nuclear exclusion. Using minimal geometric assumptions, we derive closed-form expressions linking experimentally measurable parameters, including target coverage, volume ratio, and size, to phagocytic capacity and a normalized axial separation that quantifies nuclear accommodation. The model predicts a size- and curvature-independent geometric criterion for nuclear involvement applicable to both spherical and planar targets. These results establish nuclear geometry as a fundamental physical bottleneck in phagocytosis and provide a quantitative framework for interpreting stalled engulfment and nuclear deformation-dependent responses.

The internal dynamics of liquid-liquid phase-separated systems are governed primarily by polymer packing, excluded-volume effect, and interactions between polymers and encapsulated macro-molecules. Although one immediate effect of such a constrained microenvironment is diffusion limitation, it remains unclear whether encapsulated macromolecules can also exhibit phase composition-specific functional behaviour that is not observable in a well-mixed aqueous environment. In this regard, different phases in a phase-separated environment can be accessed via a phase diagram that demarcates the region between two-phase (droplets) and one-phase (polymer-rich, no droplets) regimes. While the two-phase region is heterogeneous, most previous work on encapsulating functional macromolecules in phase-separated droplets uses a single point from the phase diagram. This leaves a clear gap in understanding on how the function scales across this landscape of droplets and identifying regions advantageous for the encapsulated macromolecule and its function. Here, using the Spinach light-up RNA aptamer, we show that RNA function does not scale uniformly across the phase diagram. We show that RNA can exhibit phase composition-specific functional behaviour due to constraints imposed by the internal microenvironment of phase-separated droplets. Furthermore, using variants of the Spinach aptamer, we show that fluorescence activity differences among the variants vary differently with phase-separation regimes across the phase map, suggesting that some regions of the phase diagram can confer a selective advantage. Our results highlight the potential of liquid-liquid phase-separated internal microenvironments in guiding the differentiation of functional RNA variants, which could serve as a physical selection pressure in pre-cellular evolution.

The human myometrium undergoes a dramatic transformation during pregnancy, shifting from quiescence to highly synchronised contractility. Understanding this transition is crucial for addressing pathologies such as preterm labour and dystocia (ineffective labour). We present a multi-scale Functional Tissue Unit (FTU) model allowing us to investigate how tissue-level excitability emerges from single-cell electrophysiology. We propose a heterogeneity-driven selection mechanism, wherein a sub-population of cells with high intrinsic excitability dynamically emerges as pace-makers. This active process complements passive depolarisation by interstitial cells, allowing spontaneous excitation to arise without a fixed anatomical pacemaker. Stochastic simulations produced an average burst frequency of 0.047 Hz ({approx}2.8 bursts per minute), closely consistent with clinical measurements of 2-3 contractions per minute during active labour, and demonstrated that this function is robust to spatial topological changes. Furthermore, implementation of inflammation-induced remodelling simulations successfully linked molecular-level changes to a preterm labour phenotype. This model provides a platform for investigating uterine contractility and serves as a component for future whole-organ Physiome models.