Srivastava, N. — Page 2 | bioRxiv Science

bioRxiv2019

The Piezo channel is used by migrating cells to sense compressive load

Migrating cells face varied mechanical and physical barriers in physiological environments, but how they sense and respond to them remains to be fully understood. We used a custom-built cell squasher to apply uniaxial pressure to Dictyostelium cells migrating under soft agarose. Within 10 seconds of application, loads of as little as 100 Pa cause cells to move using blebs instead of pseudopods. Cells lose volume and surface area under pressure and their actin dynamics are perturbed. Myosin-II is recruited to the cortex, potentially increasing contractility and so driving blebbing. The blebbing response depends on extra-cellular calcium, is accompanied by increased cytosolic calcium and largely abrogated in null mutants of the Piezo stretch-operated channel. We propose that migrating cells sense mechanical force through mechano-sensitive channels, leading to an influx of calcium and cortical recruitment of myosin, thus re-directing the motile apparatus to produce blebs rather than pseudopods.

biophysics↗

bioRxiv2016

Probing the effect of uniaxial compression on cell migration

The chemical, physical and mechanical properties of the extra-cellular environment have a strong effect on cell migration. Aspects such as pore-size or stiffness of the matrix influence the selection of the mechanism used by cells to propel themselves, including pseudopod or blebbing. How a cell perceives its environment, and how such a cue triggers a change in behaviour are largely unknown, but mechanics is likely to be involved. Because mechanical conditions are often controlled by modifying the composition of the environment, separating chemical and physical contributions is difficult and requires multiple controls. Here we propose a simple method to impose a mechanical compression on individual cells without altering the composition of the gel. Live imaging during compression provides accurate information about the cells morphology and migratory phenotype. Using Dictyostelium as a model, we observe that a compression of the order of 500 Pa flattens the cells under gel by up to 50%. This uniaxial compression directly triggers a transition in the mode of migration, from primarily pseudopodial to bleb driven, in less than 30 sec. This novel device is therefore capable of influencing cell migration in real time and offers a convenient approach to systematically study mechanotransduction in confined environments.

biophysics↗