Biomechanics and biophysics of cancer cells☆

Abstract

The past decade has seen substantial growth in research into how changes in the biomechanical and biophysical properties of cells and subcellular structures influence, and are influenced by, the onset and progression of human diseases. This paper presents an overview of the rapidly expanding, nascent field of research that deals with the biomechanics and biophysics of cancer cells. The review begins with some key observations on the biology of cancer cells and on the role of actin microfilaments, intermediate filaments and microtubule biopolymer cytoskeletal components in influencing cell mechanics, locomotion, differentiation and neoplastic transformation. In order to set the scene for mechanistic discussions of the connections among alterations to subcellular structures, attendant changes in cell deformability, cytoadherence, migration, invasion and tumor metastasis, a survey is presented of the various quantitative mechanical and physical assays to extract the elastic and viscoelastic deformability of cancer cells. Results available in the literature on cell mechanics for different types of cancer are then reviewed. Representative case studies are presented next to illustrate how chemically induced cytoskeletal changes, biomechanical responses and signals from the intracellular regions act in concert with the chemomechanical environment of the extracellular matrix and the molecular tumorigenic signaling pathways to effect malignant transformations. Results are presented to illustrate how changes to cytoskeletal architecture induced by cancer drugs and chemotherapy regimens can significantly influence cell mechanics and disease state. It is reasoned through experimental evidence that greater understanding of the mechanics of cancer cell deformability and its interactions with the extracellular physical, chemical and biological environments offers enormous potential for significant new developments in disease diagnostics, prophylactics, therapeutics and drug efficacy assays.

An historical perspective on cell mechanics

“…Previously, it has been shown that mechanical force delivered by the AFM tip can induce various chemo-mechanical responses [167][168][169]. In recent work, it has also been shown that the mechanical environment of many cell types (including cancer and stem cells) can be used to control and alter gene expression and differentiation pathways [21-25, 164,170,171]. We now have the tools to measure mechanical properties, and we have the tools to alter the mechanical environment of a cell or even deliver well-defined forces to a cell.…”

Recent advances in microfluidic techniques for single-cell biophysical characterization

“…[1][2][3][4] The unique biochemical and biophysical properties enable a cell to fulfill its specific functions and adapt to its surrounding environment. Physiological changes within the cells are accompanied by chemical and physical modifications and reorganization.…”

“…The lack of clinical relevance is due to the very low measurement throughput and tedious operation procedures of conventional techniques for measuring the biophysical properties of cells. 4,[7][8][9] Compared to conventional techniques, the advantages of small sample volume, integration capability, biocompatibility and fast response make microfluidic technologies attractive for studying cells. Recent decades have witnessed significant advances of microfluidic technologies for biochemical characterization of cells.…”

“…Microfluidic techniques for studying the roles of mechanical and electrical stimuli in the regulation of differentiation, migration, and metabolic activities have been reviewed elsewhere. 3,4,13 …”

Cyclic voltammetry: A new strategy for the evaluation of oxidative damage to bovine insulin

“…[1][2][3][4] Once oxidative damage occurs in proteins, their corresponding functions reduce or disappear, thereby inducing aging, diabetes, cancer, cardiovascular disease, and other pathological conditions. [5][6][7] The inherent correlations between the aforementioned diseases and protein oxidative damage have been widely confirmed and have aroused wide attention. 1,[8][9][10] Investigation into the oxidative damage mechanism of proteins not only benefits to clarify protein functions, but also contributes to disease diagnosis, prevention and treatment.…”