Nanomechanics of Cells and Biomaterials Studied by Atomic Force Microscopy

Abstract

The behavior and mechanical properties of cells are strongly dependent on the biochemical and biomechanical properties of their microenvironment. Thus, understanding the mechanical properties of cells, extracellular matrices, and biomaterials is key to understanding cell function and to develop new materials with tailored mechanical properties for tissue engineering and regenerative medicine applications. Atomic force microscopy (AFM) has emerged as an indispensable technique for measuring the mechanical properties of biomaterials and cells with high spatial resolution and force sensitivity within physiologically relevant environments and timescales in the kPa to GPa elastic modulus range. The growing interest in this field of bionanomechanics has been accompanied by an expanding array of models to describe the complexity of indentation of hierarchical biological samples. Furthermore, the integration of AFM with optical microscopy techniques has further opened the door to a wide range of mechanotransduction studies. In recent years, new multidimensional and multiharmonic AFM approaches for mapping mechanical properties have been developed, which allow the rapid determination of, for example, cell elasticity. This Progress Report provides an introduction and practical guide to making AFM-based nanomechanical measurements of cells and surfaces for tissue engineering applications.

Nanoindentation of Soft Biological Materials

“…Overall, compared with the Oliver–Pharr model based on elastic–plastic deformation (or the “correction” based on viscous-elastic–plastic deformation), the Hertz and Sneddon models, based on elastic contact, may dominate the literature for soft biomaterials due to their simplicity and widespread application [86]. The comparisons between the Oliver–Pharr method and Hertz contact model are summarized in Table 1, in which some aspects, such as tip selection and control mode, will be further discussed in the next section.…”

“…Aside from the theories based on adhesive contact, some methods for non-adhesive contact have been employed for POC determination, and summed up in the literature [86,87]. These include, but are not limited to, visual inspection [112], model fitting [105], extrapolation [112,113], and Bayesian analysis [114].…”

“…Schematic diagram of the adhesion in AFM nanoindentation, in which the red line is the approach and the blue line is the retract curve. Reproduced with permission from [86]. …”

Quantitative mechanics of 3D printed nanopillars interacting with bacterial cells

“…To prevent the substrate from affecting the final results, the indentation depth should be less than 10% of the pillar height. 64,65 In all of our experiments, the indentation depth was 5 nm, which is <7% of the minimum height of the pillars.…”

A Cost-Effective Method to Immobilize Hydrated Soft-Tissue Samples for Atomic Force Microscopy

“…For over two decades, atomic force microscopy (AFM) has been the gold standard for measuring the mechanical properties of both biomaterials and cells at high spatial resolution and force sensitivity within physiologically relevant environments (13). However, while determining the mechanical properties of hard scaffolds is relatively straightforward, mechanical testing of soft tissue scaffolds poses significant challenges, the primary of which is sample mounting.…”