Study Of Local Hydrodynamic Environment Of Cell-substrate Adhesion And Atherosclerotic Plaque

Nowadays, caner and atherosclerosis are two major killers for human beings in theworldwide, which are hard to conquer. Therefore, tumor cells metastasis in blood vessel andatherosclerosis plaque stability in complex flow became the focus of researchers' concern. Asboth the two phenomenon are related with blood flow, we intend to study the localhydrodynamic environment, and the followings are our main focus in the dissertation:1) Thelocal hydrodynamic environment in the process of leukocyte-mediated melanoma adhesion onendothelium cells;2) The local hydrodynamic environment around atherosclerosis plaqueunder helical flow.Dong's lab developed a "two step" hypothesis for tumor cells metastasis that leukocytecould facilitate melanoma adhesion on endothelium cells under flow, which is affected bydifferent shear flow and promoted by fibrin(ogen). In order to deeply understand thebiomechanics behind "two step" hypothesis, we improved our side-view μPIV system andsuccessfully measured the flow velocity profile around multi-cells system which is adhered tothe substrate under different shear flow. Combined with computational fluid dynamicssimulation, we found that:1) In an isolated cell system, cell length, cell height and celldeformability degree all affected local flow environment, and local shear rate had the highestsensitivity to cell length;2) In two cell system, besides cell deformability, the relativepositions between two adhered cells contributed to local shear rate change, and leukocyte withsmaller diameter was affected more. Since fibrin concentration increase in tumormicroenvironment, we measured local flow profiles around adhered leukocyte and melanomain the presence of immobilized fibrin(ogen) or soluble fibrin(ogen) under different shear flow.The results showed that under different shear flow:1) Endothelium cells monolayer changedthe patterns of flow profile in the bottom of side-view flow chamber, and also increased thewall shear rates;2) The effects of immobilized fibrin on the flow environment around adheredmelanomas were higher than those on adhered leukocytes;3) Soluble fibrin(ogen) influencedthe relative shear rates variations above adhered leukocyte and melanoma at differentleukocyte-melanoma positions, and soluble fibrin made the curves of relative shear ratesbecame flatter. Soluble fibrin increased the collision frequency between leukocytes, melanoma and endothelium cells, affected contact time and contact area among those cells,resulting in the enhancement of adhered melanomas on endothelium cells and their retentiontime.The extreme stress usually occurs on the shoulder of atherosclerosis plaque due to flowshear stress. The growth of plaque changes the blood vessel stenosis, therefore affects thelocal hydrodynamic environment. Besides, the components of plaque are considered as a keyfactor for its stability. We take advantage of ADINA FSI modulus to simulate plaque stabilityin the presence of helical flow, the results indicated that:1) Helical flow had influence onstress distribution and stress extreme value, deformation gradient of blood vessel, and relativeflow parameters in blood vessel with different stenosis to some extent;2) Helical flow hadhigher influence on moderately narrow blood vessel than severe narrow blood vessel;3)Stress distribution, deformation gradient and relative flow parameters showed differencesbetween blood vessel with different stenosis.