Modeling Receptor-Ligand Mediated Adhesion in Nanoindentation of Cells
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0975-DD09-11
Modeling Receptor-Ligand Mediated Adhesion in Nanoindentation of Cells Zhang Chunyu, and Zhang Yongwei Materials Science and Engineering, National University of Singapore, 10 Kent Ridge Crescent, 119260, Singapore
ABSTRACT The specific adhesion mediated by receptor-ligand binding in the nanoindentation of cells was studied by using a continuum-kinetics approach. It was found that the adhesion force only causes a shift to the indentation loading curve whereas the unloading curve is tilted downward by the adhesion force, resulting in a hysteresis. Parametric studies were conducted to investigate how experimental conditions influence the adhesion force. It was found that the maximum adhesion force is sensitive to the geometry of the indenter but insensitive to the indentation depth and the mechanical properties of cells. It was also shown that the dependence of the adhesion force on the loading and unloading rates is controlled by the association rate of the receptorligand binding, leading to three well-defined regimes. INTRODUCTION The adhesion of cells to other cells or to an extracellular matrix is of great importance in many biological processes and biotechnological applications [1, 2]. This non-covalent but highly specific interaction is mediated by the binding of surface proteins (receptors) with the proteins (ligands) on the surface of other cells or in the extracellular matrix [2]. To obtain quantitative information on the adhesion strength, various experimental approaches such as shear flow assays [3], centrifugal assays [4] and micropipettes [5], have been developed to study the collective behavior of the receptor-ligand binding. Recently, nanoindentation using atomic force microscopy (AFM) has been emerging as another powerful tool not only to characterize the mechanical properties of cells but also to investigate the cellular adhesion even on singlemolecule level [6-8]. By using the nanoindentation test, the modulus of a cell can be extracted from the indentation loading curve by fitting with a contact model and the adhesion force can be determined from the unloading curve. However, whether or not the modulus extraction is affected by the adhesion force is not clear since the contact models, such as the Hertz theory [9] or the SneddonÃs solution [10] assume an absence of adhesion force. In addition, the value of the adhesion force may also be affected by many experimental parameters such as the indentation depth, the geometry of the indenter and the loading and unloading rates of the indentation test. Therefore, an investigation of the adhesion force in the nanoindentation test of cells is necessary in order to reliably estimate the mechanical properties and the adhesion strength of cells from the indentation data.
THEORY In the present study, the cell was modeled as a soft elastic half-space (to represent the homogenized cytoplasm and the cytoskeletal filament network) covered by an elastic shell (to represent the cell membrane). These assumptions can be approximately met by limiting the e
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