Tissue mechanics, an important regulator of development and disease

Abstract

A growing body of work describes how physical forces in and around cells affect their growth, proliferation, migration, function and differentiation into specialized types. How cells receive and respond biochemically to mechanical signals is a process termed mechanotransduction. Disease may arise if a disruption occurs within this mechanism of sensing and interpreting mechanics. Cancer, cardiovascular diseases and developmental defects, such as during the process of neural tube formation, are linked to changes in cell and tissue mechanics. A breakdown in normal tissue and cellular forces activates mechanosignalling pathways that affect their function and can promote disease progression. The recent advent of high-resolution techniques enables quantitative measurements of mechanical properties of the cell and its extracellular matrix, providing insight into how mechanotransduction is regulated. In this review, we will address the standard methods and new technologies available to properly measure mechanical properties, highlighting the challenges and limitations of probing different length-scales. We will focus on the unique environment present throughout the development and maintenance of the central nervous system and discuss cases where disease, such as brain cancer, arises in response to changes in the mechanical properties of the microenvironment that disrupt homeostasis. This article is part of a discussion meeting issue ‘Forces in cancer: interdisciplinary approaches in tumour mechanobiology’.

Interactions between Muscle and Bone—Where Physics Meets Biology

“…The last three decades have seen an emancipation of mechanobiology as a modulator of cellular biochemistry, which is highly relevant for tissue formation already early in development and throughout the adult life cycle for tissue maintenance, remodeling, and regeneration [1,19]. Mechanical forces and cellular deformations can now be measured down to the molecular level, and their biological consequences are being unraveled, demonstrating a new world of interaction between physics and cell biology [4,20,21].…”

“…Evolution has provided multiple pathways for the mutual interaction of muscle and bone in order to adapt the stability of the skeleton and muscle to the forces needed for locomotion and environmental challenges. Recent information indicates that the reciprocity of mechanochemical interaction is extremely dynamic, including the cellular, the tissue, and the organismic level [1][2][3][4]. Intrinsic as well as extrinsic forces such as gravity generate adaptive changes of tissues, which modulate muscle power and fracture resistance.…”

Neuron and astrocyte aggregation and sorting in three-dimensional neuronal constructs

“…Our in silico model is predicated on the existence of attractive and repulsive forces that govern collective cell movements in neuronal 3D cultures. These forces may be a combination of cell–cell interactions, cell–ECM interactions, chemotaxis, and other processes 35 . Both neurons and astrocytes express cadherins and integrins, which may mediate cell–cell and cell–ECM interactions, respectively 36 – 38 .…”

Mechanobiology of Autophagy: The Unexplored Side of Cancer

“…As a physical boundary between the cell and the environment, the plasma membrane constitutes a prime location for mechanosensation and mechanotransduction (170,171). The poorly extensible lipid bilayer (rupture occur at only 3-5% area expansion) is mechanically supported by the actin cortex, which, thanks to its active dynamics, absorbs a great portion of applied stress, control folding and unfolding of plasma membrane into and out of membrane reservoirs and facilitates vesicle trafficking and fusion.…”