Mechanotransduction as a major driver of cell behaviour: mechanisms, and relevance to cell organization and future research

Abstract

How do cells process environmental cues to make decisions? This simple question is still generating much experimental and theoretical work, at the border of physics, chemistry and biology, with strong implications in medicine. The purpose of mechanobiology is to understand how biochemical and physical cues are turned into signals through mechanotransduction. Here, we review recent evidence showing that (i) mechanotransduction plays a major role in triggering signalling cascades following cell–neighbourhood interaction; (ii) the cell capacity to continually generate forces, and biomolecule properties to undergo conformational changes in response to piconewton forces, provide a molecular basis for understanding mechanotransduction; and (iii) mechanotransduction shapes the guidance cues retrieved by living cells and the information flow they generate. This includes the temporal and spatial properties of intracellular signalling cascades. In conclusion, it is suggested that the described concepts may provide guidelines to define experimentally accessible parameters to describe cell structure and dynamics, as a prerequisite to take advantage of recent progress in high-throughput data gathering, computer simulation and artificial intelligence, in order to build a workable, hopefully predictive, account of cell signalling networks.

Is There a Need for a More Precise Description of Biomolecule Interactions to Understand Cell Function?

“…As was recently reviewed [61], this kinetic description provided a substantial help to the analysis of complex biological phenomena. An early example is the attachment of blood leukocytes to the vessel walls as an early step of inflammation.…”

“…Cell cohesion obviously needs stable attachments between structural molecules. Cell communication with the outer world relies on the adhesion to other cells or surfaces, and recognition of soluble or surface-bound mediators with hundreds of membrane receptors [61]. Generation and propagation of intracellular signaling events relies on the formation and dissociation of multimolecular complexes [62,63].…”

“…The aforementioned methods are subject to two kinds of limitations (see [61] for a recent discussion). First, important cell functions such as adhesion or migration on surfaces are mediated by membrane receptors and surface-bound molecules.…”

“…The laminar flow chamber (LFC, Figure 5) has been used for nearly three decades to study the formation and rupture of single molecular attachments between surface-bound molecules. This technique was extensively described in a previous review [82] and important results obtained with the LFC were recently reviewed [61]. Briefly, receptor-bearing cells or microspheres are driven along surfaces sparsely coated with ligand molecules with a low shear hydrodynamic flow, which imparts to them a typical velocity on the order of tens of µm/s.…”

“…It is, therefore, useful to discuss available information about the physiological relevance of the force dependence of ligand receptor bonds. In addition to a recent review [61], we shall briefly mention some important examples:…”