To pull or be pulled: parsing the multiple modes of mechanotransduction

Abstract

A cell embedded in a multicellular organism will experience a wide range of mechanical stimuli over the course of its life. Fluid flows or neighboring cells actively exert stresses on the cell, while the cell’s environment presents a set of passive mechanical properties that constrain its physical behavior. Cells respond to these varied mechanical cues through biological responses that regulate activities such as differentiation, morphogenesis, and proliferation, as well as material responses involving compression, stretching, and relaxation. Here, we break down recent studies of mechanotransduction into categories based on the input mechanical stimuli acting upon the cell and the output response of the cell. This framework provides a useful starting point for identifying overlaps in molecular players and sensing modalities, and it highlights how different timescales involved in biological and material responses to mechanical inputs could serve as a means for filtering important mechanical signals from noise.

YAP/TAZ as mechanosensors and mechanotransducers in regulating organ size and tumor growth

“…Within cells, the intracellular force/tension generated by the actin‐myosin cytoskeleton, as well as the surface tension generated at the membrane, provide intrinsic mechanisms to sense and respond to physical perturbations. Indeed, the classic finding of mesenchymal stem cells developing into specific cell lineages as a function of substrate stiffness, and different tissues and organs adopting distinct physical niches for their differentiation, all highlight that in addition to biochemical signals, the physical environment controls cell fates and organ formation [28–30].…”

The (dys)functional extracellular matrix

“…Integrin type and density determine the cell adhesion affinity for, and mechanical sensing of, the ECM [3,7,8]. The most commonly studied ECM mechanical properties are substrate stiffness (a structural property) and elastic modulus (a material property) (Table 1) [4,5,9]. Cells sense substrate stiffness primarily via integrin-dependent actomyosin contraction (Fig.…”

Techniques to stimulate and interrogate cell–cell adhesion mechanics

“…The negative pressure forces the suspended cell to attach to the tip of the micropipette as a microscope imaging system records cell deformation during the process [118]. This simple procedure has been used to investigate membrane elasticity [119,120], to quantify mechanical and material properties of single cells and cell nuclei [121,122], to measure molecular adhesions between pairs of cells [123,124], and to study mechanotransduction within single cells [125,126]. The technique imposes large strains on cells, and as a result is incompatible with some cell types [27].…”