Interaction Between Jet And Cell Membrane In Sonoporation And Morphological Behavior Of Endothelial Tissue

Gene delivery technique aiming at cell reprogramming is a powerful tool in biological medical engineering.The sonoporation technique developed in re-cent years has been becoming a frontier and promising area for its advantages in biological security.Unlike biochemical metho1s,the sonoporation opens the cell membrane by the interaction of the bubble and the cell membrane un-der the action of ultrasound,which can be automatically repaired on the cell membrane based on its self-healing mechanism,thereby achieving transmem-brane transport of drugs.As a toxic and side effect-free method with superior biocompatibilit.y,it has received intensive attention since its first introductiou and already been widely and effectively applied to various kin1s of cells.How-ever,there are still many open questions in its mechnobiological mechanisms,which have greatly limited the further development and clinic application of this method.The complicated multiscale problems involved in the interaction between jets or shear flows and cellular membranes still remain a hotspot in academic research.As a systematic method of gene delivery,sonoporation technique entails several additional biophysical processes,including the opening of cell junction between vascular endothelial cells by external force to ensure the successful passing of drugs in the blood and delivery to the focus.Endothelial tissues under stress and changes in local mechanical properties may lead to the mor-phological changes iin the bloo1 vessel,whose impact oin drug lelivery and human health requires further scientific evaluation.This thesis first constructs a microscopic system containing the bubble and phospholipid bilayers,studying the non-equilibrium process under the shock wave by means of Martini coarse-grained molecular dynamics.Based on the cylindrical Vertex model,this thesis also probes into the morphological changes of tlie vascular endothelial tissue caused by changes in local mechanical properties between cells.TheI main works of this thesis are outlined as follows(1)The process of jet penetration through cell membrane cauaed by the bubble collapse under the shock wave was studied by the coarse-grained molec-ular dynamics.It was found that this process was accompanied by a secondary cavitation.The secondary cavitation zone was formed near the hole on the membrane and present.ed a circula.r distribution.To quant.it.at.ively study the circular secondary cavitation zone,the dyuamic cliange of pressure field with time in the whole non-equilibrium process of the micro-system was calculated throvigh Irving-Kirkwoocd-Noll process,and the mechanism of this phenomenon was clarified by combining the pressure information obtained with Rayleigh-Plosset equation in classical nucleation theory(2)The flow fiel1 of interaction between jet and cell membrane unler the axisymmetric conditions was obtained based oin the results of coarse-grained molecular dynamic simulation.The results revealed that jet impingement is the main factor of cell membrane deformation and even rupture in this nonequilibrium process.To analyze the mechno-biological mechanisms in cellmembrane rupture,the phospholipid molecule near the central position of the cell membra.ne was selecte to estinate the thickness of membrane at this po?sition and the stretching characteristics of its two sides.The results indicat.ed that under the action of jet impingement,the membrane stretching towards the direction of jet flow was less than that on the other side of the membrane in the process of the invagination deformation of the cell membrane(3)A vascular endothelial t issue composed of txwo-cdimensional and polyg-onal elezents was constructed using the cylindrical Vertex model.By defining the appropriate energy form of the elements iin the network(edge,face and face angle),the interaction between cells can be depicted,and the morpho-logical characteristics of the whole endothelial tissue obtained.Based on this model,this thesis studied the deformation of tubular shell under the effect of embedded contractile ring.It was shown that as the embedded contraction strengthels,the tubular shell was prole to local bulge ald evel to abrupt collapse when the contraction intensity reached a certain critical value.This thesis presented a further analysis of the impact of geometric nonlinearity and constitutive nonlinearity of materials on the deformation of tubular shell.