The Biophysics of Cancer: Emerging Insights from Micro‐ and Nanoscale Tools

Abstract

Cancer is a complex and dynamic disease that is aberrant both biologically and physically. There is growing appreciation that physical abnormalities with both cancer cells and their microenvironment that span multiple length scales are important drivers for cancer growth and metastasis. The scope of this review is to highlight the key advancements in micro‐ and nanoscale tools for delineating the cause and consequences of the aberrant physical properties of tumors. Herein, the following three important physical aspects of cancer are focused: 1) solid mechanical properties, 2) fluid mechanical properties, and 3) mechanical alterations to cancer cells. Beyond posing physical barriers to the delivery of cancer therapeutics, these properties are also known to influence numerous biological processes, including cancer cell invasion and migration leading to metastasis, and response and resistance to therapy. There is a comment on how micro‐ and nanoscale tools have transformed the fundamental understanding of the physical dynamics of cancer progression and their potential for bridging toward future applications at the interface of oncology and physical sciences.

Biophysics involved in the process of tumor immune escape

“…Tap mode is the commonly used mode, like a blind man touching an elephant, slowly stroking the surface of an object, and a three-dimensional image of its surface can be visualized. In the tap mode, the tip force can be inferred from the cantilever displacement of the atomic force microscope using Hooke’s law) Equation (1) and ( Beshay et al., 2022 ). F = k△x F is the force acting on the tip of the cantilever, k is the cantilever stiffness, and ▵x is the displacement of the tip.…”

“…Micropipettes are frequently used to examine deformability and viscoelasticity of individual cells. The main building blocks are relatively simple (shown in Figure 8 A) ( Beshay et al., 2022 ; Mohammadalipour et al., 2018 ). Usually an optical microscope, a microfluidic track, a small pressure pump, or a pipette are used in this method, and this method is important to detect deformability and viscoelasticity of cells ( Houk et al., 2012 ; Esteban-Manzanares et al., 2017 ; Guilak et al., 2000 ; Nava et al., 2008 ).…”

“…It is well-known that tumors are stiffer than normal tissue because of the high fibrosis at the tumor tissue, the stiff stroma of the tumor cells, and the elevated expression of cytoskeleton-related proteins ( Beshay et al., 2022 ). Correlation stiffness maps of biopsies obtained from different locations of breast tumors show a progressive increase in extracellular matrix (ECM) stiffness from the center to the periphery ( Paszek et al., 2005 ) ( Figure 2 A).…”

Multiplexed Detection of Molecular Interactions with DNA Origami Engineered Cells in 3D Collagen Matrices

“…Cell interactions are highly affected by their microenvironments, including the physical and biochemical properties of the surrounding extracellular matrix (ECM). , Living systems are complex and difficult to control and interrogate efficiently at cellular length scales, making it difficult to study detailed mechanisms efficiently in animal models. 3D tissue models are useful surrogates for animal models that recapitulate key aspects of living tissues while enabling control over the environment with simpler measurement readouts; hence, these are useful systems to study underlying mechanisms of cell response in physiologically relevant microenvironments.…”

Multiplexed Detection of Molecular Interactions with DNA Origami Engineered Cells in 3-D Collagen Matrices

“…Cell interactions are highly affected by their microenvironments, including the physical and biochemical properties of the surrounding extracellular matrix (ECM) [10,11] . Living systems are complex and difficult to control and interrogate efficiently at cellular length scales making it difficult to study detailed mechanisms efficiently in animal models.…”