Abstract

Almost all biological cells in living tissues exert and experience forces that influence biological function. When subjected to an exogenous electric field, mechanical forces operate on cells, its constituents, and interfaces with the environment. Many issues about force generation and dynamics, the distance over which a force exerts its influence and how cells convert an electrical excitation into a mechanical deformation, are not well understood from general first-principles physics. The electric field at the interface between cells is not only the driving force for the polarization and conduction phenomena but also induces simultaneously a mechanical stress field. Within the extremely heterogeneous multicellular structure of biological materials (BM), theoretical models and experimental techniques to understand and control their local electromechanical response in BM grow space. In recent years, biophysicists have begun to uncover the important time and length scales that mediate force propagation in BM. In this perspective review, the multiscale modelling approaches and experimental probes for the application of an electromagnetic field to exert mechanical forces upon polarizable BM are reported with special emphasis on the control of forces at the cell and tissue levels. Modelling is based on a multicellular assembly exchanging charges and stresses with the environment. Here, we shall restrict to coarse-graining models since the resulting computational complexity quickly becomes overwhelming. Such work can pave the way for a deeper understanding of how physical forces influence biological functions.

Highlights

  • Biological materials (BM) such as eukaryotic cells and tissues are extremely heterogeneous and structured at many length scales. Such materials are deformable by external stresses, electric or magnetic fields, or even by thermal fluctuations which can be described from a soft condensed matter perspective

  • One can note the large difference in absolute values of the surface charge density for the situation found at lower frequencies for which large values of Maxwell stress tensor (MST) are close to the poles of the spherical reference cell and very weak at the equator as might be expected. This observation fits with the pearl chain effect, i.e., biological particles immersed in liquid media align themselves and form pearl chains under an applied electromagnetic field when the field strength is greater than a certain minimum value

  • A physics perspective in this field will likely be to imagine numerical tools that lower the level of complexity of living biological materials (BM) by keeping only the relevant and most important structural features, and how to think about the collective mechanics of individual cells organized in a hierarchical structure which is stimulated with an electric field

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Summary

Context and motivation

Biological materials (BM) such as eukaryotic cells and tissues are extremely heterogeneous and structured at many length scales. A partial motivation for this report is to summarize and highlight recent major advances in electromechanobiology that have paved the way for new phenomena and technologies useful for manipulation of BM at cellular and tissue levels. Throughout this perspective at the interfaces of applied physics and biology, we will highlight the importance and benefits of multiscale models of multicellular force in BM as leverage to be used for manipulating and engineering synthetic BM, both for therapeutic applications and basic biological studies. After exploring the insights provided by these examples, we discuss some of the most recent multiphysics coarse-graining approaches that are opening up opportunities in achieving great sensitivity of relaxation, electric field induced transmembrane voltage (ITV), electroporation (EP), and membrane disruption consequent on the variation of the operating frequency, shape, and surface charge, and we briefly offer perspective comments and describe relevant challenges on the current trends in this field of research

ANALYTICAL FORMULATIONS OF FORCES
Background
CS modelling
Cell electropermeabilization
RECENT ADVANCES AND HIGHLIGHTS IN FORCE MEASUREMENT IN THE LAB
Introduction
Measurement of cell and tissue deformation
Cell perforation
MULTISCALE PHYSICS OF INTERCELLULAR FORCES IN TISSUES
Stress distribution dependence on material distribution and properties
Modelling cell perforation
LOOKING AHEAD IN ELECTROMECHANOBIOLOGY
Theoretical perspectives
Experimental perspectives
Findings
Clinical perspectives
Full Text
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