Mechanics Of Rolling Adhesion Of Cell Under Shear Flow

As the basic structural unit of life,cells play an important role in a series of physiological responses,such as immune response,cancer metastasis,and endocytosis of vesicles.Among them,the adhesion of cell-cell and cell-extracellular matrix under blood flow is a critical issue in many basic physiological and pathological processes,such as leukocyte exosmosis,in which circulating white blood cells are summoned along the bloodstream to damaged or inflamed tissues.In this case,the rolling leukocytes are sufficiently subjected to the force from the bloodstream to interact with the ligands on the endothelial surface to form adhesion molecule pairs.in view of the specific recognition ability of leukocyte rolling adhesion,artificial nanocarriers with specific recognition were designed,which could have potential application value in blood circulation targeted drug delivery.Therefore,a full understanding of the mechanical mechanism of rolling adhesion of cells in fluid environment will contribute greatly to basic biological processes and biomedical applications,in particular,it is of great value to understand the physiological phenomena such as immune response under leukocytes mediated by adhesion molecules.Although a large number of theoretical,simulation and experimental studies have focused on the specific cell-basal adhesion behavior and its mechanism,most of these studies have focused on the cell adhesion process in the relatively static environment,where cells are often subjected to hydrodynamic shock from the blood flow.And relatively less research about the role of cell specificity rolling adhesion of concerns are focused on only one type of adhesion molecules,based on many experiments proved that choosing and integrin in white blood cells exist in the shear flow rolling adhesion synergies,but chose and integrin synergy cells and rolling dynamics mechanism has not yet been fully resolved.Therefore,how to coupling the action of fluid dynamics,cell specific adhesion and the kinematic behavior of cell body is the key to understand the related biological behavior of cells in laminar flow environment,and is also the core scientific problem to be solved in this thesis.Specifically,a mechanical model of cell rolling mediated by catch bond in shear flow is proposed,and the model is optimized based on the competitive reaction mechanism of double adhesion molecules(integrins and selectins),and the stochastic dynamics analysis of the specific adhesion process of membrane encapsulation of flexural stiffness vesicles is carried out.The specific innovative achievements are as follows:Firstly,we focus on the background that the catch-slip behavior of selectin bonds can be responsible for the shear threshold effect.We consider the random reaction of catch bond and the hydrodynamic impact of shear flow,and establish a cell adhesion mechanics model based on energy conservation.Our results suggest that this flowenhanced stability of rolling adhesion is attributed to the competition between stochastic reactions of bonds and dynamics of cell rolling,instead of force lengthening the lifetime of catch bonds,thereby challenging the current view of underlying mechanism of this flow-enhanced adhesion phenomenon.Moreover,the loading history of flow defining bistability of cell adhesion in shear flow is predicted.Secondly,we consider that studies have shown that leukocyte capture to the vascular endothelium occurs via a two-step mechanism,rolling adhesion migration and firm adhesion to the vascular wall,mediated by integrins and selectins.Here we present a mechanical model on selectin-and integrin-jointly mediated rolling adhesion of leukocyte in shear flow,by considering two pairs' binding/unbinding events as Markov processes and describing kinetics of leukocyte by the approach of continuum mechanics approach.Through examining the dynamics of leukocyte rolling as a function of relative fraction of selectin and integrin pairs,we show that,during recruitment,the elongation of intermittent low affinity selectin bonds consuming the kinetic energy of rolling leukocyte decelerates the rolling speed and enables the high affinity integrin pairs to form strong bonds,therefore achieving the arrestment of leukocyte(firm adhesion).Finally,considered the stochastic dynamic adhesion endocytosis of the vesicle membrane to the membrane under thermal fluctuation,and the local adhesion molecular aggregation causes uneven vesicle membrane bending stiffness,based on markov process,through the mesh point of vesicle membrane,established variable stiffness vesicle dynamic parcel model and the Monte Carlo simulation program of the package process.Our results predict the influence of different encapsulation points on the completion time,and the theoretical predicted probability distribution of encapsulation life over time is in good agreement with the simulation results,which verifies the spontaneous rotation of vesicles observed in the experiment and is consistent with the static analysis of the encapsulation path(from soft to hard)of vesicles.