How the mechanobiome drives cell behavior, viewed through the lens of control theory

Abstract

Cells have evolved sophisticated systems that integrate internal and external inputs to coordinate cell shape changes during processes, such as development, cell identity determination, and cell and tissue homeostasis. Cellular shape-change events are driven by the mechanobiome, the network of macromolecules that allows cells to generate, sense and respond to externally imposed and internally generated forces. Together, these components build the cellular contractility network, which is governed by a control system. Proteins, such as non-muscle myosin II, function as both sensors and actuators, which then link to scaffolding proteins, transcription factors and metabolic proteins to create feedback loops that generate the foundational mechanical properties of the cell and modulate cellular behaviors. In this Review, we highlight proteins that establish and maintain the setpoint, or baseline, for the control system and explore the feedback loops that integrate different cellular processes with cell mechanics. Uncovering the genetic, biophysical and biochemical interactions between these molecular components allows us to apply concepts from control theory to provide a systems-level understanding of cellular processes. Importantly, the actomyosin network has emerged as more than simply a 'downstream' effector of linear signaling pathways. Instead, it is also a significant driver of cellular processes traditionally considered to be 'upstream'.

Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies

“…In order to change shape, cells need to sense and respond to external mechanical stimulus and forces. These molecules are thought to be part of the mechanobiome, which includes molecules ranging from cell adhesion to ECM to the contractile molecules in the cytosol (Kothari et al, 2019). Together they form a network of proteins, where some act either as a sensors or actuators.…”

“…Together they form a network of proteins, where some act either as a sensors or actuators. Some of the proteins, like non-muscle myosin II, can act both as a sensor and an actuator, and further link to other proteins like scaffolding proteins and transcription factors (Luo et al, 2012;Kothari et al, 2019). Notably, the actomyosin network is a significant driver of cellular processes by regulating gene expression and has been implicated as an important regulator in angiogenesis (Angulo-Urarte et al, 2018;Kothari et al, 2019).…”

The distinct roles of myosin IIA and IIB under compression stress in nucleus pulposus cells

“…The actomyosin system plays a leading role in the response to mechanical stimuli, including stretch, compression and shear forces, as well as internally generated tension and strain. 11,12 The actomyosin system consists of actin and myosin, which form stress fibres for generating contractile forces. The members of the myosin family are grouped into more than 30 classes that have different distributions and play diverse functions.…”

May mechanobiology work forcefully for you

“…As muscles move, nerves stretch and compress. Mechanobiology offers insight about such mechanics through numerous nondestructive techniques [1][2][3] . Yet existing methods are hard for non-experts to use well.…”