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Thiagarajan, R.

Publications and source records attributed to Thiagarajan, R..

2 recordsLinked to original sources

Control and mechanisms of pulsatile flows in epithelial monolayers

Collective motions of epithelial cells in vivo are essential for morphogenesis in developmental biology. Tissues elongate, contract, flow, and oscillate, thus sculpting embryos. These tissue level dynamics are known, but the physical mechanisms at the cellular level are unclear, with various behaviors depending on the tissues and species. Moreover, investigations on in vitro tissue behavior usually focus on only one type of cell dynamics and use diverse theoretical approaches, making systematic comparisons between studies challenging. Here, we show that a single epithelial monolayer of Madin Darby Canine Kidney (MDCK) cells can exhibit two types of local tissue kinematics, pulsations and long range coherent flows. We analyzed these distinct motions by using quantitative live imaging. We also report that these motions can be controlled with internal and external cues such as specific inhibitors, and friction modulation of the substrate by microcontact printing method. We further demonstrate with a unified vertex model that both behaviors depend on the competition between velocity alignment and random diffusion of cell polarization. When alignment and diffusion are comparable, a pulsatile flow emerges, whereas the tissue undergoes long-range flows when velocity alignment dominates. We propose that environmental friction, acto-myosin distributions, and cell polarization kinetics are important in regulating the dynamics of tissue morphogenesis.

biophysics

Cell motion as a stochastic process controlled by focal contacts dynamics.

Directed cell motion is essential in physiological and pathological processes such as morphogenesis, wound healing and cancer spreading. Chemotaxis has often been proposed as the driving mechanism, even though evidence of long-range gradients is often lacking in vivo. By patterning adhesive regions in space, we control cell shape and the associated potential to move along one direction in another mode of migration coined ratchetaxis. We report that focal contacts distributions collectively dictate cell directionality, and bias is non-linearly increased by gap distance between adhesive regions. Focal contact dynamics on micro-patterns allow to integrate these phenomena in a consistent model where each focal contact can be translated into a force with known amplitude and direction, leading to quantitative predictions for cell motion in every condition. Altogether, our study shows how local and minutes timescale dynamics of focal adhesions and their distribution lead to long term cellular motion with simple geometric rules.

biophysics