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Flow dynamics analyses of pathophysiological liver lobules using porous media theory

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Acta Mechanica Sinica 2017年第4期33卷 823-832页

作者： Jinrong Hu Shouqin Lü Shiliang Feng mian long Center of Biomechanics and Bioengineering Key Laboratory of Microgravity (National Microgravity Laboratory) Beijing Key Laboratory of Engineered Construction and Mechanobiology Institute of Mechanics Chinese Academy of Sciences School of Engineering Science University of Chinese Academy of Sciences

Blood flow inside the liver plays a key role in hepatic functions, and abnormal hemodynamics are highly correlated with liver diseases. To date, the flow field in an elementary building block of the organ, the liver lobule,is difficult to determine experimentally in humans due to its complicated structure, with radially branched microvasculature and the technical difficulties that derive from its geometric constraints. Here we established a set of 3D computational models for a liver lobule using porous media theory and analyzed its flow dynamics in normal, fibrotic,and cirrhotic lobules. Our simulations indicated that those approximations of ordinary flow in portal tracts（PTs） and the central vein, and of porous media flow in the sinusoidal network, were reasonable only for normal or fibrotic *** modified with high resistance in PTs and collateral vessels inside sinusoids were able to describe the flow features in cirrhotic lobules. Pressures, average velocities, and volume flow rates were profiled and the predictions compared well with experimental data. This study furthered our understanding of the flow dynamics features of liver lobules and the differences among normal, fibrotic, and cirrhotic lobules.

关键词： porous cirrhotic collateral ordinary permeability tracts constraints branched porosity inlet

Mechanokinetics of receptor-ligand interactions in cell adhesion

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Acta Mechanica Sinica 2015年第2期31卷 248-258页

作者： Ning Li Shouqin Lü Yan Zhang mian long Key Laboratory of Microgravity(National Microgravity Laboratory) Center of Biomechanics and Bioengineeringand Beijing Key Laboratory of Engineered Construction and MechanobiologyInstitute of MechanicsChinese Academy of Sciences

Receptor-ligand interactions in blood flow are crucial to initiate such biological processes as inflammatory cascade,platelet thrombosis,as well as tumor *** mediate cell adhesion,the interacting receptors and ligands must be anchored onto two apposing surfaces of two cells or a cell and a substratum,i.e.,two-dimensional（2D）binding,which is different from the binding of a soluble ligand in fluid phase to a receptor,i.e.,three-dimensional（3D） *** numerous works have been focused on3 D kinetics of receptor-ligand interactions in the immune system,2D kinetics and its regulations have been less understood,since no theoretical framework or experimental assays were established until *** only does the molecular structure dominate 2D binding kinetics,but the shear force in blood flow also regulates cell adhesion mediated by interacting receptors and ***,we provide an overview of current progress in 2D binding and regulations,mainly from our *** issues of theoretical frameworks,experimental measurements,kinetic rates and binding affinities,and force regulations are discussed.

关键词： Receptor-ligand interactions Selectins β_2 integrins 2D binding kinetics

Quantifying cell binding kinetics mediated by surface-bound blood type B antigen to immobilized antibodies

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Chinese Science Bulletin 2008年第23期53卷 3634-3641页

作者： LI BaoXia CHEN Juan long mian National Microgravity Laboratory and Center of Biomechanics and Bioengineering Institute of Mechanics Chinese Academy ofSciences Beijing 100190 China

Cell adhesion is crucial to many biological processes, such as inflammatory responses, tumor metastasis and thrombosis formation. Recently a commercial surface plasmon resonance (SPR)-based BIAcore biosensor has been extended to determine cell binding mediated by surface-bound bio-molecular interactions. How such cell binding is quantitatively governed by kinetic rates and regulating factors, however, has been poorly understood. Here we developed a novel assay to determine the binding kinetics of surface-bound biomolecular interactions using a commercial BIAcore 3000 bio-sensor. Human red blood cells (RBCs) presenting blood group B antigen and CM5 chip bearing immobilized anti-B monoclonal antibody (mAb) were used to obtain the time courses of response unit, or sensorgrams, when flowing RBCs over the chip surface. A cellular kinetic model was proposed to correlate the sensorgrams with kinetic rates. Impacts of regulating factors, such as cell concentration, flow duration and rate, antibody-presenting level, as well as pH value and osmotic pressure of suspending medium were tested systematically, which imparted the confidence that the approach can be applied to kinetic measurements of cell adhesion mediated by surface-bound biomolecular interactions. These results provided a new insight into quantifying cell binding using a commercial SPR-based BIAcore biosensor.

关键词：生物传感器细胞动力模式细胞学构成模式

Spreading of human neutrophils on an ICAM-1-immobilized substrate under shear flow

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Chinese Science Bulletin 2012年第7期57卷 769-775页

作者： ZHAN DongYing ZHANG Yan long mian Key Laboratory of Microgravity National Microgravity Laboratory and Center of Biomechanics and BioengineeringInstitute of MechanicsChinese Academy of SciencesBeijing 100190China

Neutrophil (PMN) spreading on endothelium, mediated by the interactions between surface-bound β2 integrin and intercellular adhesion molecule-1 (ICAM-1) in the inflammatory cascade, is crucial for PMN post-adhesion and trans-migration in blood flow. The underlying mechanisms by which shear flow regulates PMN spreading dynamics are not well understood. Here, a parallel-plate flow chamber assay was applied to quantify the time course of PMN adhesion and spreading on an ICAM-1-immobilized substrate. Two types of shear flow, steady flows at shear stresses of 0.2, 0.5, and 1 dyne/cm2 and stepwise flows at 0, 1, and 10 dyne/cm2, were used to elucidate the impact of shear flow on cell adhesion and spreading. The number of adhered PMNs, the fraction of spreading PMNs and the projected area of spread PMNs were determined and were found to correlate with the distribution of surface-bound β2 integrin subunit (CD11a, CD11b, or CD18). The results indicate that PMN spreading on an ICAM-1 substrate is bi-directionally regulated under shear flow. CD11a, CD11b and CD18 subunits of β2 integrin contribute distinctly to PMN spreading on ICAM-1 substrates. This work provides new insights into understanding PMN spreading on the endothelium, mediated by β2 integrin and ICAM-1 under shear flow.

关键词： ICAM-1 中性粒细胞剪切流场基板传播细胞间粘附分子1 扩散动力学血管内皮细胞

Mechanomics： an emerging field between biology and biomechanics

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Protein & Cell 2014年第7期5卷 518-531页

作者： Jiawen Wang Dongyuan Lu Debin Mao mian long Center for Biomechanics and Bioengineering and Key Laboratory of Microgravity Institute of Mechanics Chinese Academy of Sciences Beijing 100190 China

Cells sense various in vivo mechanical stimuli, which initiate downstream signaling to mechanical forces. While a body of evidences is presented on the impact of limited mechanical regulators in past decades, the mechanisms how biomechanical responses globally affect cell function need to be addressed. Complexity and diversity of in v/vo mechanical clues present dis- tinct patterns of shear flow, tensile stretch, or mechanical compression with various parametric combination of its magnitude, duration, or frequency. Thus, it is required to understand, from the viewpoint of mechanobiology, what mechanical features of cells are, why mechanical properties are different among distinct cell types, and how forces are transduced to down- stream biochemical signals. Meanwhile, those in vitro isolated mechanical stimuli are usually coupled together in vivo, suggesting that the different factors that are in effect individually could be canceled out or orchestrated with each other. Evidently, omics analysis, a powerful tool in the field of system biology, is advantageous to combine with mechanobiology and then to map the fullset of mechanically sensitive proteins and transcripts encoded by its genome. This new emerging field, namely mechanomics, makes it possible to elucidate the global responses under systematically-varied mechanical stimuli. This review discusses the current advances in the related fields of mechanomics and elaborates how cells sense external forces and activate the biological responses.

关键词： mechanomics mechanobiology proteomics transcriptomics

Simulation and prediction of membrane fusion dynamics

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Theoretical & Applied Mechanics Letters 2022年第1期12卷 49-55页

作者： Zhi Zheng Shouqin Lü mian long Center of Biomechanics and Bioengineering Key Laboratory of Microgravity(National Microgravity Laboratory)Beijing Key Laboratory of Engineered Construction and Mechanobiologyand CAS Center for Excellence in Complex System MechanicsInstitute of MechanicsChinese Academy of SciencesBeijing 100190China School of Engineering Science University of Chinese Academy of SciencesBeijing 100049China

Membrane fusion is an important process by which biological membranes perform their life activities. Simulations show that the membrane fusion process happens mainly through three pathways, where the Stalk-Pore hypothesis, in which two membranes come into close contact to form a stalk to a hemifusion intermediate, and then the fusion pore opens to achieve completely fusion, is widely accepted, and there exist two free energy barriers that break the current structural steady state for lipid rearrangement. Factors of lipid composition, mechanical environment, protein and ion have regulatory roles in the membrane fusion process by effecting membrane curvature structurally and the free energy barriers from energetic perspective. Meanwhile, many theoretical models, represented by the Helfrich model, have been proposed to predict the membrane fusion process. In this paper, we review the research process of membrane fusion and mainly introduce the dynamics of membrane fusion, regulation factors and typical theoretical models.

关键词： Membrane fusion Hemifusion intermediates Fusion pathway Regulation Helfrich model

SJ-10 Recoverable Satellite for Space Microgravity Experiments

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空间科学学报 2020年第5期40卷 648-654页

作者： HU Wenrui KANG Qi DUAN Enkui long mian Institute of Mechanics Chinese Academy of SciencesBeijing 100190 School of Engineering Science University of Chinese Academy of SciencesBeijing 100049 Institute of Zoology Chinese Academy of SciencesBeijing 100101

SJ-10 is a recoverable scientific experiment satellite specially for the space experiments of microgravity physics science and space life *** mission was officially started on 31 December 2012,and the satellite was launched on 6 April *** paper introduces briefly the SJ-10 mission,the progress of SJ-10 engineering and the project constitution of sciences experiments onboard *** purpose of this mission is to discover the law of matter movement and the rule of life activity that cannot be discovered on the ground due to the existence of gravity,and to know the acting mechanism on organisms by the complex radiation of space that cannot be simulated on the ground.

关键词： Microgravity physics Space life science Space microgravity experiments Recoverable satellite

Multi-scale molecular dynamics simulations and applications on mechanosensitive proteins of integrins

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Chinese Physics B 2021年第3期30卷 1-8页

作者： Shouqin Lu Qihan Ding Mingkun Zhang mian long Center of Biomechanics and Bioengineering Key Laboratory of Microgravity(National Microgravity Laboratory)Beijing Key Laboratory of Engineered Construction and Mechanobiologyand CAS Center for Excellence in Complex System MechanicsInstitute of MechanicsChinese Academy of Sciences(CAS)Beijing 100190China School of Engineering Science University of Chinese Academy of SciencesBeijing 101408China Chongqing Engineering Research Center of High-Resolution and 3D Dynamic Imaging Technology Chongqing Institute of Green and Intelligent TechnologyChinese Academy of SciencesChongqing 400714China

Molecular dynamics simulation(MDS)is a powerful technology for investigating evolution dynamics of target proteins,and it is used widely in various fields from materials to *** mini-review introduced the principles,main preforming procedures,and advances of MDS,as well as its applications on the studies of conformational and allosteric dynamics of proteins especially on that of the mechanosensitive *** perspectives were also *** review could provide clues in understanding the potentiality of MD simulations in structure–function relationship investigation of biological proteins.

关键词： molecular dynamics simulations mechanosensitive protein allosteric dynamics integrin

Probe stiffness regulates receptor-ligand bond lifetime under force

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Science China(Physics,Mechanics & Astronomy) 2011年第5期54卷 923-929页

作者： ZHANG Yan LüShouQin &long mian Key Laboratory of Microgravity Institute of MechanicsChinese Academy of SciencesBeijing 100190China National Microgravity Laboratory and Center of Biomechanics and Bioengineering Institute of MechanicsChinese Academy of SciencesBeijing 100190China

Receptor-ligand bond dissociation under applied force is crucial to elucidate its biological functionality when the molecular bond is usually connected to a mechanical probe. While the impact of probe stiffness, k, on bond rupture force has recently at- tracted more and more attention, the mechanism of how it affects the bond lifetime, however, remains unclear. Here we quanti- fied the dissociation lifetime of selectin-ligand bond using an optical trap assay with low stiffness ranging from 3.5×10^-3 to 4.7×10^-2 pN/nm. Our results indicated that bond lifetime yielded distinct distributions with different probe stiffness, implying the stochastic feature of bond dissociation. It was also found that the mean lifetime varied with probe stiffness and that the catch bond nature was visualized at k≥3.0×10^-2 pN/nm. This work furthered the understanding of the forced dissociation of se- lectin-ligand bond at varied probe stiffness, which is physiologically relevant to the tethered rolling of leukoeytes under blood flow.

关键词： probe stiffness bond lifetime optical trap