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Shiladitya Banerjee

Publications and source records attributed to Shiladitya Banerjee.

26 records · Page 2Linked to original sources

Controlling cell-matrix traction forces by extracellular geometry

We present a minimal continuum model of strongly adhering cells as active contractile isotropic media and use the model to study the effect of the geometry of the adhesion patch in controlling the spatial distribution of traction and cellular stresses. Activity is introduced as a contractile, hence negative, spatially homogeneous contribution to the pressure. The model shows that patterning of adhesion regions can be used to control traction stress distribution and yields several results consistent with experimental observations. Specifically, the cell spread area is found to increase with substrate stiffness and an analytic expression for the dependence is obtained for circular cells. The correlation between the magnitude of traction stresses and cell boundary curvature is also demonstrated and analyzed.

cond-mat.soft↗

Cadherin-Based Intercellular Adhesions Organize Epithelial Cell-Matrix Traction Forces

Cell--cell and cell-matrix adhesions play essential roles in the function of tissues. There is growing evidence for the importance of crosstalk between these two adhesion types, yet little is known about the impact of these interactions on the mechanical coupling of cells to the extracellular-matrix (ECM). Here, we combine experiment and theory to reveal how intercellular adhesions modulate forces transmitted to the ECM. In the absence of cadherin-based adhesions, primary mouse keratinocytes within a colony appear to act independently, with significant traction forces extending throughout the colony. In contrast, with strong cadherin-based adhesions, keratinocytes in a cohesive colony localize traction forces to the colony periphery. Through genetic or antibody-mediated loss of cadherin expression or function, we show that cadherin-based adhesions are essential for this mechanical cooperativity. A minimal physical model in which cell--cell adhesions modulate the physical cohesion between contractile cells is sufficient to recreate the spatial rearrangement of traction forces observed experimentally with varying strength of cadherin-based adhesions. This work defines the importance of cadherin-based cell--cell adhesions in coordinating mechanical activity of epithelial cells and has implications for the mechanical regulation of epithelial tissues during development, homeostasis, and disease.

physics.bio-ph↗

Contractile stresses in cohesive cell layers on finite-thickness substrates

Using a minimal model of cells or cohesive cell layers as continuum active elastic media, we examine the effect of substrate thickness and stiffness on traction forces exerted by strongly adhering cells. We obtain a simple expression for the length scale controlling the spatial variation of stresses in terms of cell and substrate parameters that describes the crossover between the thin and thick substrate limits. Our model is an important step towards a unified theoretical description of the dependence of traction forces on cell or colony size, acto-myosin contractility, substrate depth and stiffness, and strength of focal adhesions, and makes experimentally testable predictions.

cond-mat.soft↗

Scaling of Traction Forces with Size of Cohesive Cell Colonies

To understand how the mechanical properties of tissues emerge from interactions of multiple cells, we measure traction stresses of cohesive colonies of 1-27 cells adherent to soft substrates. We find that traction stresses are generally localized at the periphery of the colony and the total traction force scales with the colony radius. For large colony sizes, the scaling appears to approach linear, suggesting the emergence of an apparent surface tension of order 1E-3 N/m. A simple model of the cell colony as a contractile elastic medium coupled to the substrate captures the spatial distribution of traction forces and the scaling of traction forces with the colony size.

cond-mat.soft↗

Generic phases of cross-linked active gels: Relaxation, Oscillation and Contractility

We study analytically and numerically a generic continuum model of an isotropic active solid with internal stresses generated by non-equilibrium `active' mechano-chemical reactions. Our analysis shows that the gel can be tuned through three classes of dynamical states by increasing motor activity: a constant unstrained state of homogeneous density, a state where the local density exhibits sustained oscillations, and a steady-state which is spontaneously contracted, with a uniform mean density.

cond-mat.soft↗

Substrate rigidity deforms and polarizes active gels

We present a continuum model of the coupling between cells and substrate that accounts for some of the observed substrate-stiffness dependence of cell properties. The cell is modeled as an elastic active gel, adapting recently developed continuum theories of active viscoelastic fluids. The coupling to the substrate enters as a boundary condition that relates the cell's deformation field to local stress gradients. In the presence of activity, the coupling to the substrate yields spatially inhomogeneous contractile stresses and deformations in the cell and can enhance polarization, breaking the cell's front-rear symmetry.

q-bio.CB↗

Motor-driven Dynamics of Cytoskeletal FIlaments in Motility Assays

We model analytically the dynamics of a cytoskeletal filament in a motility assay. The filament is described as rigid rod free to slide in two dimensions. The motor proteins consist of polymeric tails tethered to the plane and modeled as linear springs and motor heads that bind to the filament. As in related models of rigid and soft two-state motors, the binding/unbinding dynamics of the motor heads and the dependence of the transition rates on the load exerted by the motor tails play a crucial role in controlling the filament's dynamics. Our work shows that the filament effectively behaves as a self-propelled rod at long times, but with non-Markovian noise sources arising from the coupling to the motor binding/unbinding dynamics. The effective propulsion force of the filament and the active renormalization of the various friction and diffusion constants are calculated in terms of microscopic motor and filament parameters. These quantities could be probed by optical force microscopy.

cond-mat.stat-mech↗

Instabilities and Oscillations in Isotropic Active Gels

We present a generic formulation of the continuum elasticity of an isotropic crosslinked active gel. The gel is described by a two-component model consisting of an elastic network coupled frictionally to a permeating fluid. Activity is induced by active crosslinkers that undergo an ATP-activated cycle and transmit forces to the network. The on/off dynamics of the active crosslinkers is described via rate equations for unbound and bound motors. For large activity motors yield a contractile instability of the network. At smaller values of activity, the on/off motor dynamics provides an effective inertial drag on the network that opposes elastic restoring forces, resulting in spontaneous oscillations. Our work provides a continuum formulation that unifies earlier microscopic models of oscillations in muscle sarcomeres and a generic framework for the description of the large scale properties of isotropic active solids.

cond-mat.soft↗