Biology subjects

Murrell, M.

Publications and source records attributed to Murrell, M..

5 recordsLinked to original sources

bioRxiv2026

Tissue geometry encodes a surface tension gradient that drives epithelial renewal

The mammalian intestinal epithelium renews itself every few days through coordinated cell movement and extrusion along the crypt-villus axis, yet how these processes are physically organized across intact tissue remains unknown. Using long-term live imaging of intact intestinal tissue, nuclear strain mapping, and targeted perturbations of cell-cell adhesion, actomyosin contractility, and extracellular matrix adhesion, we find that epithelial cells experience a graded mechanical landscape encoded by villus geometry; tension is highest at the villus tip and decays toward the base. This tissue-scale tension gradient, generated by E-cadherin-mediated adhesion and actomyosin contractility, is the dominant predictor of collective cell velocity, outperforming force magnitude and cell density. Artificial re-establishment of a tension gradient is sufficient to reorient epithelial migration, whereas disruption of the gradient arrests both cell movement and extrusion. Epithelial renewal further requires a precise balance between this tension gradient and extracellular matrix-derived friction; excessive friction uncouples migration from extrusion, leading to pathological cell accumulation. Together, these findings reveal that intestinal epithelial homeostasis is organized by a geometry-encoded mechanical gradient that coordinates collective cell motion, extrusion, and tissue repair through a single tissue-scale framework.

cell biology↗

bioRxiv2026

Mechanical organization yields degenerate dissipation beyond linear response

In non-equilibrium (active) systems, increased driving is commonly assumed to produce proportionally greater energy dissipation. Using picowatt-sensitive calorimetry, entropy-production analysis, rheology, and microscopy in reconstituted actomyosin networks, we show that this relationship breaks down as the material reorganizes under motor activity. Dissipation initially increases with myosin abundance but subsequently decreases despite continued network stiffening, indicating that energetic cost becomes regulated by the evolving mechanical state rather than actuator abundance alone. Comparing catch-bond (-actinin) and slip-bond (fascin) crosslinked networks reveals that bond mechanics shift the critical motor concentration at which this transition occurs, marking the onset of state-dependent energy conversion. Although these networks generate distinct active stresses and mechanical states, they can exhibit comparable dissipation rates, revealing that state-dependent energy conversion can produce degenerate dissipation, whereby mechanically distinct states exhibit similar energetic costs. These findings demonstrate that dissipation in active materials is governed not only by the magnitude of driving but also by the mechanical state that emerges in response to that driving, providing an experimental example of state-dependent energy conversion far from equilibrium.

biophysics↗

bioRxiv2024

Caging of membrane-to-cortex attachment proteins can trigger cellular symmetry breaking

To migrate, divide, and change shape, cells must regulate the mechanics of their periphery. The cell surface is a complex structure that consists of a thin, contractile cortical actin network tethered to the plasma membrane by specialized membrane-to-cortex attachment (MCA) proteins. This active and constantly fluctuating system maintains a delicate mechanochemical state which permits spontaneous polarization and shape change when needed. Combining in silico, in vitro, and in vivo experiments we show how membrane viscosity and MCA protein length regulate cortical dynamics. We reveal a novel mechanism whereby caging of linker proteins in the actin cortex allows for the amplification of small changes in these key parameters, leading to major alterations of cortical contractility. In cells, this mechanism alone gives rise to symmetry breaking phenomena, suggesting that local changes in lipid composition, in combination with the choice of MCA proteins, contribute to the regulation of cellular morphogenesis and function.

biophysics↗

bioRxiv2024

Energy partitioning in the cell cortex

Living systems are driven far from thermodynamic equilibrium through the continuous consumption of ambient energy1. In the cell cortex, this energy is invested in the formation of diverse patterns in chemical and mechanical activities, whose unique spatial and temporal dynamics determine cell phenotypes and behaviors2-6. However, how cells partition internal energy between chemical and mechanical work is unknown7-9. Here we measured the entropy production rate (EPR) of both the chemical and mechanical subsystems of the cell cortex across a broad range of periodic patterns as the system is driven further from equilibrium via manipulation of the Rho GTPase pathway, which controls cortical actin filaments (F-actin) and myosin-II. We find that at lower levels of Rho GAP (GTPase activating protein) expression, which produce pulses or "choppy" Rho and F-actin waves, energy is comparably partitioned between the chemical and mechanical subsystems and is subject to the constraint of Onsager reciprocity. Within the range of reciprocity, the EPR is maximized in choppy waves that resemble the waves associated with cell division3,10. However, as the cortex is driven even further from equilibrium into elaborate labyrinthine or spiral traveling wave trains via increased GAP expression, reciprocity is broken, marking an increasingly differential partitioning of energy and an uncoupling of chemical and mechanical activities. We further demonstrate that energy partitioning and reciprocity are determined by the competition between the timescales of chemical reaction and mechanical relaxation. These results indicate that even within coupled cellular subsystems, both the relative proportions of energy partitioned to each subsystem and the ultimate phenotypic outcome vary dramatically as a function of the overall energy investment.

biophysics↗

bioRxiv2020

A molecular clock controls periodically driven cell migration in confined spaces

Navigation through dense, physically confining extracellular matrix is common in invasive cell spread and tissue re-organization, but is still poorly understood. Here, we show that this migration is mediated by cyclic changes in the activity of a small GTP-ase RhoA, dependent on the oscillatory changes in the activity and abundance of the RhoA Guanine Exchange Factor, GEF-H1, triggered by a persistent increase in the intracellular Ca2+ levels. We show that the molecular clock driving these cyclic changes is mediated by two coupled negative feedback loops, dependent on the microtubule dynamics, with the frequency that can be experimentally modulated based on a predictive mathematical model. We further demonstrate that an increasing frequency of the clock translates into a faster cell migration within physically confining spaces. This work lays the foundation for a better understanding of the molecular mechanisms dynamically driving cell migration in complex environments.

systems biology↗