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Nanomechanical Characterization of Biological Cells

Accurate characterization on the mechanics of biological cells, such as cell-to-cell adhesion and cellular contraction forces, is of paramount importance for understanding their physiological and pathological processes. In our laboratory, we have recently developed several novel tools, including i) Atomic Force Microscopy Force Spectroscopy, ii) Nanobiomechanical Tester, iii) Optical Tweezers, and iv) Confocal Reflection Interference Contrast Microscopy, that allow structural and biomechanical characterization of biological cells and tissues, associated with various diseases [1]. In this talk, I will briefly present the first two techniques and their applications in biomedicine.

Cell adhesion is a complex process regulated by a number of surface proteins as well as cytoskeleton structure. The former has been recognized to contribute mainly on molecular force, while latter governs the mechanical properties (e.g. elasticity) involved in cell adhesion. The importance of characterizing cell surface molecular binding events altered by protein ligation as well as cell elasticity changed due to cytoskeletal re-organization has recently been highlighted by our recent study [2]. Atomic force microscopy force spectroscopy (AFM-FS) has been demonstrated as a powerful tool for the quantitative study of both single cell elasticity and surface molecular binding. We have applied AFM-FS to measure the detachment energy, unbinding force between two adherent HK2 cells as well as the elasticity and viscoelasticity of the cells [3-4].

This talk will also report a novel technique to quantify contraction force in cells embedded in a 3-D matrix environment by combining nanobiomechanical measurements of cell-embedded hydrogels with theoretical analysis of the gel mechanics [5]. Measurement of cell contraction forces is essential for many biomedical research fields such as wound healing, inflammation, tissue engineering and regenerative medicine. The force elicited by human fibroblast contraction in response to a stimulus was assessed by the method in a non-destructive manner. Therefore, this novel nanobiomechanical technique can be potentially developed to test the effects of pharmacological interventions or bioengineering methods on contraction force in different cell types.

[1] Q. Wang, K. Manmi, & K. K. Liu, 2015, Interface focus, 5 (5). 20150018.
[2] E. Siamantouras, K. K. Liu et al, 2014, FEBS Letters, 588, 1173-117
[3] E. Siamantouras, K. K. Liu et al, 2016, Nanomedicine: Nanotechnology, Biology, and Medicine, 12 (4), 1013–1021
[4] L. Liu, J. Yu, & K. K. Liu, 2018, Physical Review Letters (to be published)
[5] T. Jin, K. K. Liu et al, 2015, Journal of The Royal Society Interface, 12 (106), 2014136