A Review of Single-Cell Adhesion Force Kinetics and Applications

Abstract

Cells exert, sense, and respond to the different physical forces through diverse mechanisms and translating them into biochemical signals. The adhesion of cells is crucial in various developmental functions, such as to maintain tissue morphogenesis and homeostasis and activate critical signaling pathways regulating survival, migration, gene expression, and differentiation. More importantly, any mutations of adhesion receptors can lead to developmental disorders and diseases. Thus, it is essential to understand the regulation of cell adhesion during development and its contribution to various conditions with the help of quantitative methods. The techniques involved in offering different functionalities such as surface imaging to detect forces present at the cell-matrix and deliver quantitative parameters will help characterize the changes for various diseases. Here, we have briefly reviewed single-cell mechanical properties for mechanotransduction studies using standard and recently developed techniques. This is used to functionalize from the measurement of cellular deformability to the quantification of the interaction forces generated by a cell and exerted on its surroundings at single-cell with attachment and detachment events. The adhesive force measurement for single-cell microorganisms and single-molecules is emphasized as well. This focused review should be useful in laying out experiments which would bring the method to a broader range of research in the future.

Adhesion of Neurons and Glial Cells with Nanocolumnar TiN Films for Brain-Machine Interfaces

“…spreading of cells in contact with a surface due to surface tension effects when cells are considered liquid-like [40]) since the force spectroscopy microscope actively pushes the cell onto the electrode substrate with a constant setpoint of 500 pN, and then sustains the reached z-position for the adhesion time of either 5 s or 30 s, respectively. The results were normalized to the cell-material contact area (see Materials and Methods) to exclude the influence of sheer cell size, which likely correlates with the number of formed adhesion points and therewith adhesion force itself [41]. As expected [42], we found higher values of the cell-substrate adhesion force for both cell lines on all materials for the longer contact time.…”

Single-cell adhesivity distribution of glycocalyx digested cancer cells from high spatial resolution label-free biosensor measurements

“…Except for some cell types, for example, immune cells [2] , [3] and circulating tumor cells [4] , [5] , cells need to adhere to the extracellular matrix or to the surface of another cell to survive. The adhesion is influenced by both intracellular and extracellular factors such as the cytoskeleton, membrane-bound adhesion proteins, and elements of the glycocalyx [1] , [5] , [6] , [7] , [8] . The glycocalyx is a multifunctional, carbohydrate-rich layer covering the cell surface.…”

Population distributions of single-cell adhesion parameters during the cell cycle from high-throughput robotic fluidic force microscopy

“…Typical parameters of FD-curves were evaluated for the general population, and lognormal distribution was the adequate fit for these characteristic parameters. The lognormal nature of the obtained data is an important finding since most prior literature, with a relatively low number of single-cell adhesion measurements, treats experimental data as normally distributed or without the intention of addressing the nature of adhesion parameter distribution 7 , 19 , 36 , 39 . Since in a lognormal distribution a significant portion of the cells has parameters far from the mode, conclusions based on adhesion data of a low number of cells (or treating the population as normally distributed) can be heavily misleading.…”

“…As mentioned, previous SCFS techniques did not produce a sufficient data output, and even low-cell-number SCFS studies suggested that the measured SCFS parameters do not follow a specific distribution. Namely, the maximal single-cell adhesion force ( F max ), adhesion energy ( E max ), and the traveled distance of the cantilever, with respect to the surface at F max ( D max ) were typically investigated 7 , 10 , 19 , 21 , 36 . Importantly, low throughput does not allow studying the distributions of large cell populations or revealing possible subpopulations.…”