Force sensing on cells and tissues by atomic force microscopy

Abstract

Biosensors are aimed to detect tiny physical and chemical stimuli in biological systems. Physical forces are ubiquitous, being implied in all cellular processes, including cell adhesion, migration, and differentiation. Given the strong interplay between cells and their microenvironment, the extracellular matrix (ECM), the structural and mechanical properties of the ECM play an important role in the transmission of external stimuli to single cells within the tissue. Vice versa, also cells themselves use self-generated forces to probe the biophysical properties of the ECM. ECM mechanics influences cell fate, regulates tissue development and show peculiar features in health and disease conditions of living organisms. Force sensing in biological systems is therefore crucial to dissect and understand complex biological processes, such as mechanotransduction. Atomic Force Microscopy (AFM), which can both sense and apply forces at the nanoscale, with sub-nanoNewton sensitivity, represents an enabling technology and a crucial experimental tool in biophysics and mechanobiology. In this work, we report on the application of AFM to study of biomechanical fingerprints of different components of biological systems, such as the ECM, the whole cell, and cellular components, like the nucleus and the glycocalyx. We show that physical observables like the (spatially resolved) Young's modulus of elasticity of ECMs or cells, and the effective thickness and stiffness of the glycocalyx, can be quantitatively characterised by AFM. Their modification can be correlated to changes of the microenvironment, physio-pathological conditions, or gene regulation.

The nanomechanical fingerprint of colorectal cancer -derived peritoneal metastasis

“…The elastic properties of the ECMs were characterized through their Young’s modulus (YM) of elasticity, extracted by fitting the Hertz model [29,44] to the 20%-80% indentation range of the FCs (details in Ref. [26,28]): which is accurate as long as the indentation δ is small compared to the radius R. In Eq. (1), ν is the Poisson’s coefficient, which is typically assumed to be equal to 0.5 for in-compressible materials, and E is the YM.…”

“…The elastic properties of the ECMs were characterized through their Young’s modulus (YM) of elasticity, extracted by fitting the Hertz model 57,58 to the 20%-80% indentation range of the FCs (details in Ref. 20,22 ): …”

“…Atomic force microscopy (AFM) is a powerful and versatile tool to study biological samples at the nano-and microscale, including the quantitative investigation of their morphological and mechanical properties [19][20][21][22][23][24] . The mechanical properties of cells, ECMs and tissues can be characterized by AFM [22][23][24][25][26][27][28][29][30][31] and could constitute a unique mechanical fingerprint of cancer progression 32 .…”