Reciprocity of Cell Mechanics with Extracellular Stimuli: Emerging Opportunities for Translational Medicine

Abstract

Human cells encounter dynamic mechanical cues in healthy and diseased tissues, which regulate their molecular and biophysical phenotype, including intracellular mechanics as well as force generation. Recent developments in bio/nanomaterials and microfluidics permit exquisitely sensitive measurements of cell mechanics, as well as spatiotemporal control over external mechanical stimuli to regulate cell behavior. In this review, the mechanobiology of cells interacting bidirectionally with their surrounding microenvironment, and the potential relevance for translational medicine are considered. Key fundamental concepts underlying the mechanics of living cells as well as the extracelluar matrix are first introduced. Then the authors consider case studies based on 1) microfluidic measurements of nonadherent cell deformability, 2) cell migration on micro/nano‐topographies, 3) traction measurements of cells in three‐dimensional (3D) matrix, 4) mechanical programming of organoid morphogenesis, as well as 5) active mechanical stimuli for potential therapeutics. These examples highlight the promise of disease diagnosis using mechanical measurements, a systems‐level understanding linking molecular with biophysical phenotype, as well as therapies based on mechanical perturbations. This review concludes with a critical discussion of these emerging technologies and future directions at the interface of engineering, biology, and medicine.

Decoding Biomechanical Cues Based on DNA Sensors

“…By combining algorithms and the monitoring of microscopy, TFM is often used to study the correlated forces involved in cell adhesion and can provide mechanical mapping based on the monitoring process. However, low throughput, high technical requirements, and low spatial partitioning, low force resolution (level of nN) [ 6 ] limit these two methods, respectively. To address these limitations and bridge the gap between SMFS and TFM while leveraging the advantage of both, molecular tension sensor systems have emerged.…”

AFM‐Based Poroelastic@Membrane Analysis of Cells and its Opportunities for Translational Medicine

“…[1] In this field, biomechanical factors shape cellular function by influencing the structural integrity, morphology, and dynamics of cells and tissues. Just like D'Arcy DOI: 10.1002/smll.202303610 Wentworth Thompson famously postulated that "the form of an (biological) object is a diagram of forces" in his book On Growth and Form, [2][3][4] the mechanical behaviors of cells and tissues can be both a direct consequence, and a regulating factor of biological function and cellular architecture. [5] Biomechanics research in past decades has largely focused on mechanical behaviors at the organism and organ levels due to the lack of study tools.…”

“…[ 2 ] Thus, a deeper understanding of mechanobiology at cellular scales is crucial to understanding homeostasis in normal healthy tissues. [ 2 ] Investigating life activities at single‐cell level significantly can also benefit the reveal of the novel underpinnings regulating physiological/pathological process. [ 6 ] In recent years, thanks to the development of detection technology, the mechanics clues of cells were widely used to evaluate the pathological states as a label‐free biomarker method.…”

“…[5,6] However, many tissues and organs can be understood as complex systems that are functionally affected by physical cues at cellular scales. [2] Thus, a deeper understanding of mechanobiology at cellular scales is crucial to understanding homeostasis in normal healthy tissues. [2] Investigating life activities at single-cell level significantly can also benefit the reveal of the novel underpinnings regulating physiological/pathological process.…”

“…[6] In recent years, thanks to the development of detection technology, the mechanics clues of cells were widely used to evaluate the pathological states as a label-free biomarker method. [2,7] For example, cancer cells are characterized by uncontrollable proliferation, invasiveness, and metastatic potential, [8] and biomechanical studies at single-cell level can help understand the pathogenesis of cancer. [9] Atomic force microscopy (AFM) was widely used to detect the mechanical (elastic, viscoelastic, or poroelastic) clues of cancer at single-cell level.…”