Implications of a poroelastic cytoplasm for the dynamics of animal cell shape

Abstract

Two views have dominated recent discussions of the physical basis of cell shape change during migration and division of animal cells: the cytoplasm can be modeled as a viscoelastic continuum, and the forces that change its shape are generated only by actin polymerization and actomyosin contractility in the cell cortex. Here, we question both views: we suggest that the cytoplasm is better described as poroelastic, and that hydrodynamic forces may be generally important for its shape dynamics. In the poroelastic view, the cytoplasm consists of a porous, elastic solid (cytoskeleton, organelles, ribosomes) penetrated by an interstitial fluid (cytosol) that moves through the pores in response to pressure gradients. If the pore size is small (30-60nm), as has been observed in some cells, pressure does not globally equilibrate on time and length scales relevant to cell motility. Pressure differences across the plasma membrane drive blebbing, and potentially other type of protrusive motility. In the poroelastic view, these pressures can be higher in one part of a cell than another, and can thus cause local shape change. Local pressure transients could be generated by actomyosin contractility, or by local activation of osmogenic ion transporters in the plasma membrane. We propose that local activation of Na+/H+ antiporters (NHE1) at the front of migrating cells promotes local swelling there to help drive protrusive motility, acting in combination with actin polymerization. Local shrinking at the equator of dividing cells may similarly help drive invagination during cytokinesis, acting in combination with actomyosin contractility. Testing these hypotheses is not easy, as water is a difficult analyte to track, and will require a joint effort of the cytoskeleton and ion physiology communities.

Aquaporin-1 Promotes Angiogenesis, Fibrosis, and Portal Hypertension Through Mechanisms Dependent on Osmotically Sensitive MicroRNAs

“…A recently proposed poroelastic biophysical model of the cytoplasm allows rapid localized water transport to affect cellular shape changes on time scales relevant to these processes. 41 Regardless, the considerable effect of AQP1 knockout in our model suggests a prominent role for this protein in the pathological angiogenesis that occurs during chronic liver disease.…”

Role of cortical tension in bleb growth

“…However, this pressure could also be of osmotic origin (18). We therefore sought to test the link between bleb expansion and cortical tension.…”

Whole cell mechanics of contractile fibroblasts: relations between effective cellular and extracellular matrix moduli

“…Recent evidence shows important roles for collagenase Brownian ratchet 'motors' in the form of TIMP-2/MMP-2 assemblies on the cell surface (Saffarian et al 2004), and some hypothesize as well a role for cytoplasmic pressure gradients (Mitchison et al 2008). However, the system by which these subcellular proteins combine to endow a fibroblast with shape control and mechanical function is very much an open topic of debate (Discher et al 2009).…”