Numerical Modeling And Simulation Of Cellular Response To Mechanics Microenvironment Using Dissipative Particle Dynamics

Cell is the basic unit of life body,acting as a particularly important component when body builds up from micro to macro hierarchically.All the cells in the body are stimulated by the mechanical forces generated by the cell itself as well as extracellular environment,such as stretching,shearing,cell-cell / cell-substrate interaction and basal stiffness.Cell makes a response to maintain the basic functions,such as apoptosis,differentiation,migration,proliferation and quiescence.Cellular mechanical properties and interaction with mechanics micro-environment are the main factors affecting cell function and deciding cellular mechanical behaviors at different states of diseases.Therefore,quantifying the dynamic response of cells in a specific mechanical microenvironment plays an important role in understanding the biological behavior of cells under physiological and pathological conditions.In this dissertation,a discrete cell mechanics model is established in the framework of dissipative particle dynamics,and the deformation process and the re-arragement of cytoskeletal structure are simulated.The specific contents include the following two aspects:In order to study the interaction between cells and extracellular environment,a discrete cell mechanics model was established at the subcellular level to characterize cell mechanical behavior under tensile force.Cell membrane and nucleus envelop are simplified as shell of triangle spring network connected to beads.The radius of cell membrane is three times of that of nucleus.A bundle of actin filament is represented by mechanical spring randomly connected from one bead of cell membrane to another one.Intermediate filament is simplified as spring chains affined from bead of nucleus envelop to corresponding bead of cell membrane.Both generate a force as a function of its extension.Elastic potential energy and bending potential energy express elastic resistance to changes in bending and stretching on cell membrane as well as nucleus envelop,and total / local area constraint potential energy and volume constraint potential energy are applied to maintain the total / local area conservation and volume conservation of cell membrane and nucleus.To study mechanical response,a force is applied to 2% beads diametrically at opposite ends of a suspended cell.Our proposed mechanical model and analysis directly link the spatio-temporal complexities of cell remodeling,cytoskeletal re-orientation and mechanical properties alteration,which is consistent with the published experimental result.Concurrently,this dissertation takes some parametric investigation to study the effect of cellular coarse-grain,stretched particles number,actin filament concentration and cellular size on the cellular deformation-applied loading relationship.The results show the higher coarse-grain,the larger stretched particles number,the higher actin filament concentration and the larger cell radius,the more difficult the cell gets deformed.Atomic force microscopy is widely used as a powerful tool to study cell morphology and mechanical properties.This dissertation investigates mechanical response to a compression force on the top of a cell,corresponding to AFM probe indentation.Moreover,this dissertation studies the effects of microfilament concentration,cell radius and the role of nucleus on the mechanical response of cells.The results show the higher the intermediate filament concentration and the larger cell radius,the more difficult the cell gets deformed.When there is no nucleus,the deformation of the cell increases rapidly,which indicates that the nucleus can effectively resist compression.The mechanical model of cell proposed in this dissertation has obvious characteristics in exploring the influence of external forces on the mechanical behavior of cells and suggests an opportunity to investigate cells calibrate response to their mechanical micro-environment.