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J Cell Sci. 2019 Sep 2;132(17). pii: jcs234476. doi: 10.1242/jcs.234476.

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

Author information

1
Departments of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2
Art as Applied to Medicine, Johns Hopkins University School of Medicine, Baltimore, M 21205, USA.
3
Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
4
Departments of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA dnr@jhmi.edu.
5
Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.

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'.

KEYWORDS:

Control system; Feedback; Myosin II; Setpoint control

PMID:
31477578
DOI:
10.1242/jcs.234476

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