Force Sensing on Cells and Tissues by Atomic Force Microscopy.

Hatice Holuigue,Marcello Deraco,Marcello Guaglio,Carsten Schulte,Ewelina Lorenc,Manuela Gariboldi,Alessandro Podestà,Luca Varinelli,Matteo Chighizola

doi:10.3390/s22062197

Hatice Holuigue, Marcello Deraco + Show 7 more

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https://doi.org/10.3390/s22062197

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Abstract

Biosensors are aimed at detecting 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) and 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, cells themselves also use self-generated forces to probe the biophysical properties of the ECM. ECM mechanics influence cell fate, regulate tissue development, and show peculiar features in health and disease conditions of living organisms. Force sensing in biological systems is therefore crucial to dissecting and understanding 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 the study of biomechanical fingerprints of different components of biological systems, such as the ECM, the whole cell, and cellular components, such as the nucleus, lamellipodia and the glycocalyx. We show that physical observables such as the (spatially resolved) Young’s Modulus (YM) of elasticity of ECMs or cells, and the effective thickness and stiffness of the glycocalyx, can be quantitatively characterized by AFM. Their modification can be correlated to changes in the microenvironment, physio-pathological conditions, or gene regulation.

Highlights

In recent years, there has been a growing interest in studying the physical properties of biological samples, such as tissues, single cells, and their microenvironment, to better understand how they change during the progression of diseases, such as cancer [1–3], and how they influence each other in their mutual interaction [4–11]
The extracellular matrix (ECM), which is a fundamental component of the cell microenvironment, is a ubiquitous acellulated component present in all tissues, comprising molecules that are secreted by cells and assembled to form specific insoluble components; the ECM plays a fundamental role as a scaffold for cell growth, in the regulation of cell-cell and cell-matrix signaling, affecting cell mechanics mainly through the remodeling of the cytoskeleton, and determining cell fate [4,5,12–16]
We report on the application of Atomic Force Microscopy (AFM) to the study of biomechanical fingerprints of several components of biological systems, such as the ECM, the whole cell, and cellular components, such as the nucleus, lamellipodia and the glycocalyx

Summary

Introduction

There has been a growing interest in studying the physical properties of biological samples, such as tissues, single cells, and their microenvironment, to better understand how they change during the progression of diseases, such as cancer [1–3], and how they influence each other in their mutual interaction [4–11]. The extracellular matrix (ECM), which is a fundamental component of the cell microenvironment, is a ubiquitous acellulated component present in all tissues, comprising molecules that are secreted by cells and assembled to form specific insoluble components; the ECM plays a fundamental role as a scaffold for cell growth, in the regulation of cell-cell and cell-matrix signaling, affecting cell mechanics mainly through the remodeling of the cytoskeleton, and determining cell fate [4,5,12–16]. The physical characterization of glycocalyx has a good potential in cancer research, both as a cancer biomarker [20,25,27,30,31] and as a therapeutic target, since the reduction or degradation of the glycocalyx has been reported to reduce cell migration and suppress cell growth [32,33]

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