One-step cell biomanufacturing platform:porous gelatin microcarrier beads promote human embryonic stem cell-derived midbrain dopaminergic progenitor cell differentiation in vitro and survival after transplantation in vivo

Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.

Quantitative characterization of cell physiological state based on dynamical cell mechanics for drug efficacy indication

Cell mechanics is essential to cell development and function,and its dynamics evolution reflects the physiological state of cells.Here,we investigate the dynamical mechanical properties of single cells under various drug conditions,and present two mathematical approaches to quantitatively characterizing the cell physiological state.It is demonstrated that the cellular mechanical properties upon the drug action increase over time and tend to saturate,and can be mathematically characterized by a linear timeinvariant dynamical model.It is shown that the transition matrices of dynamical cell systems significantly improve the classification accuracies of the cells under different drug actions.Furthermore,it is revealed that there exists a positive linear correlation between the cytoskeleton density and the cellular mechanical properties,and the physiological state of a cell in terms of its cytoskeleton density can be predicted from its mechanical properties by a linear regression model.This study builds a relationship between the cellular mechanical properties and the cellular physiological state,adding information for evaluating drug efficacy.

Mechanical Force Drives the Polarization and Orientation of Collective Cells

Collective cell groups are organized to form specific patterns that play an important role in various physiological and pathological processes,such as tissue morphogenesis,wound healing,and cancer invasion.Compared to the behaviors of single cells that have been studied intensively from many aspects(cell migration,adhesion,polarization,proliferation,etc.)and at various length scales(molecular,subcellular,and cellular),the behaviors of multiple cells are less well understood,particularly from a quantitative perspective.In this talk,we present our recent studies of collective polarization and orientation of multiple cells through both experimental measurement and theoretical modeling,including cell behavior on/in 2D and 3D substrate/tissue.We find that collective cell behavior,including polarization,alignment,and migration,is closely related to local stress states in cell layers or tissue,which demonstrates the crucial role of mechanical forces in living organisms.Specifically,cells demonstrate preferential polarization and alignment along the maximum principal stress in the cell layer,and the cell aspect ratio increases with in-plane maximum shear stress,suggesting that the maximum shear stress is the underlying driving force of cell polarization and orientation.This theory of stress-driven cell behaviors of polarization and orientation provides a new perspective for understanding cell behaviors in living organisms and a guideline for tissue engineering in potential biomedical applications.Strikingly,we note that with regard to the polarization and alignment of collective cells,a typical feature of cell morphology is that the cells generally align along the edge of the pattern,which was called edge effect or boundary effect by assuming that the edge plays a role in cell alignment due to a phenomenon of chemistry.However,the edge effect is an obscure explanation.Here we showed that the edge effect could be explained by the theory of stress-driven cell behavior,i.e.,inplane stress-driven cell polarization and alignment.That is,the cell layer has a stress-free boundary condition at the edge,and thus the direction of the maximum principal stress should be precisely along the edge.According to the theory of stress-driven cell polarity,the cells then preferentially align with the edge of the cell layer,independently of the geometry of the pattern.Once there is a force-free condition at the edge or the boundary,the cells align along the edge of the pattern.Otherwise,the cell may not align with the edge;for example,the cells preferentially align in the radial direction of the wound because of the presence of the contractile force by the actin ring at the wound edge,which is in contradiction with the so-called edge effect but consistent with our theory of stress-driven cell polarity.

Role of the mechanical microenvironment in cancer development and progression

Cross-talk between tumor cells and mechanical stress in the tumor microenvironment has been shown to be involved in carcinogenesis.High mechanical stress in tumors can alter the metabolism and behaviors of cancer cells and cause cancer cells to attain cancer stem-like cell properties,thus driving tumor progression and promoting metastasis.The mechanical signal is converted into a biochemical signal that activates tumorigenic signaling pathways through mechanotransduction.Herein,we describe the physical changes occurring during reprogramming of cancer cell metabolism,which regulate cancer stem cell functions and promote tumor progression and aggression.Furthermore,we highlight emerging therapeutic strategies targeting mechanotransduction signaling pathways.

The Number of Cyclic Stretch Regulates Cellular Elasticity in C2C12 Myoblasts

Mechanical stimulations have been shown to regulate cellular mechanical properties. However, the stimulation patterns for effective regulation are as yet unclear. We investigated the effects of application of differing numbers of mechanical stimulation sets, each set consisting of 8% extension and compression to cells via deformation of cell culture elastic chamber, on cellular elasticity. Elasticity increased with only a single step-like stretch and with a single step-like stretch after 1 set of mechanical stimulation, whereas elasticity did not change with a single step-like stretch after 10 sets of mechanical stimulation. These results indicate that the increase in cellular elasticity with the single step-like stretch depends on the number of applied mechanical stimulations. Immunofluorescence staining showed that phosphorylation and dephosphorylation of myosin regulatory light chain (MRLC), which regulates intracellular contractile force and cellular elasticity, accompanied cellular elasticity changes. These findings suggest that cellular elasticity changes under cyclic and step-like stretches are mediated by MRLC.

Network pharmacology and preliminary cell screening studies on the anti-liver cancer activity of Nauclea Officinalis

Objective:To explore the mechanism of Nauclea Officinalis of anti-liver cancer effect based on network pharmacology,and to preliminarily verify anti-liver cancer activity of Nauclea Officinalis through cell screening.Methods:Network pharmacology was used to screen for common targets of Nauclea Officinalis and liver cancer,protein-protein interaction(PPI)network was constructed,and enrichment analysis and mechanism prediction were conductd.Molecular docking of main active ingredients of Nauclea Officinalis with core targets was made.Preliminary verification was performed by in vitro cell experiments such as CCK8,cell apoptosis,and PCR.Results:After the screening,14 active ingredients of Nauclea Officinalis were obtained,with 587 related targets.After mapping with liver cancer targets,there were 288 common targets,mainly including TP53,SRC,STAT3,and other core targets.Among them,compounds such as strictosamide,pumiloside and vincosamide may be potential active ingredients of Nauclea Officinalis of anti-liver cancer effect.They may participate in protein phosphorylation and negative regulation of the apoptosis process by mediating cancer pathways,PI3K/Akt and EGFR tyrosine kinase inhibitors resistance signaling pathways to play an anti-liver cancer role;molecular docking results showd that active ingredients of Nauclea Officinalis had a stable binding with liver cancer core targets;in vitro cell experiments showd that main ingredient strictosamide of Nauclea Officinalis had cytotoxicity against liver cancer cells,inhibited liver cancer cell proliferation(P<0.001),down-regulated gene expression of liver cancer HepG2 cells SRC,STAT3,MAPK3(P<0.05),and induced liver cancer cell apoptosis(P<0.001).Conclusion:This study preliminarily explores the potential mechanism of active ingredients of Nauclea Officinalis against liver cancer and its preliminary pharmacological effects,providing a theoretical basis for the study of Nauclea Officinalis of anti-liver cancer mechanism.

Effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells investigated by atomic force microscopy

Cell mechanics plays an important role in cellular physiological activities. Recent studies have shown that cellular mechanical properties are novel biomarkers for indicating the cell states. In this article, temperature-controllable atomic force microscopy(AFM) was applied to quantitatively investigate the effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells. First, AFM indenting experiments were performed on six types of human cells to investigate the changes of cellular Young's modulus at different temperatures and the results showed that the mechanical responses to the changes of temperature were variable for different types of cancer cells. Second, AFM imaging experiments were performed to observe the morphological changes in living cells at different temperatures and the results showed the significant changes of cell morphology caused by the alterations of temperature. Finally, by co-culturing human cancer cells with human immune cells, the mechanical and morphological changes in cancer cells were investigated. The results showed that the co-culture of cancer cells and immune cells could cause the distinct mechanical changes in cancer cells, but no significant morphological differences were observed. The experimental results improved our understanding of the effects of temperature and cellular interactions on the mechanics and morphology of cancer cells.

基于网络药理学和分子对接技术及实验验证探讨江南卷柏治疗喉癌的分子机制

目的探讨江南卷柏治疗喉癌的分子机制。方法根据文献报道获取江南卷柏化学成分,SwissADME数据库筛选活性成分,PharmMapper数据库筛选作用靶点。检索OMIM等数据库收集喉癌相关靶点,Venny 2.1.0在线平台将二者取交集,STRNG平台进行蛋白相互作用分析。通过DAVID数据库进行GO和KEGG富集分析,使用Cytoscape 3.8.0软件构建可视化网络。通过SYBYL-X 2.0软件进行分子对接验证。利用MTT法、Hoechst 33258染色法、Western blot进行验证。结果在分子水平上,筛选出江南卷柏活性成分110个及药物靶点82个,喉癌相关靶点1642个,交集靶点34个。GO分析得到135个条目,KEGG分析共得到88条通路。分子对接结果显示,2″,3″-二氢金连木黄酮等11个关键活性成分和MAPK1等4个核心靶蛋白有95.5%有较好的对接活性。在细胞水平上,通过MTT法细胞活力测定筛选出SM-BFRE对喉癌细胞增殖的抑制作用最强,进一步通过Hoechst 33258染色表明SM-BFRE处理后的Hep-2细胞活力下降与细胞凋亡有关,最后通过Western blot验证SM-BFRE通过抑制PI3K/Akt/NF-κB/Cox-2通路来诱导喉癌细胞发生凋亡。结论充分体现了江南卷柏治疗喉癌多成分、多靶点、多通路协同作用的特点,为深入阐明江南卷柏治疗喉癌的作用机制提供理论参考。

物理因子促进干细胞的成骨分化

背景:针对骨缺损传统修复方法的局限性,干细胞广泛应用于再生医学的研究。化学性因子是当前的研究热点,但是近年来的研究证实,国内外应用物理因素调控干细胞分化的研究不断深入,物理因子联合生物支架在骨组织工程中为解决骨缺损修复难题提供了一种新的思路和方法,具有良好的发展前景。目的:就物理因子如电磁场、超声等对干细胞成骨分化的分子机制以及信号通路的调控、在骨组织工程中应用的可行性等方面做一总结。方法:应用计算机检索中国知网和PubMed数据库中近20年的相关文献,在标题和摘要中以“干细胞,骨缺损,成骨分化,电磁场,超声,冲击波,低强度激光,机械力,骨组织工程”或“stem cell,osteoporosis,osteogenic differentiation,Electromagnetic Fields,Ultrasound,Bone Tissue Engineering”为检索词进行检索,对相关文章94篇进行综述分析。结果与结论:(1)物理因子作为一种无创、非接触的辅助疗法对骨组织工程有着显著影响,在调控干细胞的成骨分化、促进细胞的增殖以及在骨工程支架内的生存能力方面有着积极作用。(2)除了激活信号通路和成骨基因转录外,物理因子还可以改善血管化、增加支架中形成的骨的体积、面积和厚度,可以促进骨整合,提高骨支架再生健康骨组织的成功率。(3)然而,将物理因子用于骨组织工程的研究均采用不同的实验条件,如支架类型、细胞类型及干预条件等,无法直接进行比较以确定最佳参数设置,在临床应用中,这些不同干预对促进骨折愈合的有效性研究结果也缺乏一致性,因此未来还需要进一步确定物理因子用于骨组织工程的最佳参数。(4)总体而言,物理因子作为一种理想的辅助疗法,在与各种生物材料结合并应用于骨组织工程方面具有巨大的潜力。

深度学习图像识别辅助原子力显微镜单细胞力学特性精准高效探测

目的原子力显微镜(AFM)的出现为生命科学研究提供了强大工具,特别是AFM压痕实验技术已成为细胞力学特性探测的重要方法,从单细胞尺度为生理病理活动过程带来了大量新的认识,是对传统生化集群平均研究方法的有力补充。然而现有AFM压痕实验技术存在着依赖人工、效率低下等不足,严重制约了其在生命科学领域的实际应用。本文通过将光学显微成像自动目标识别技术与AFM压痕技术结合,建立了单个游离态细胞及聚团生长细胞的力学特性精准高效测量方法。方法利用YOLO深度学习算法识别出光学图像中细胞的中心部位,并通过嵌入视觉转换器(ViT)模块的双UNet神经网络模型对细胞边缘部位进行精确分割,同时采用模板匹配算法对光学图像中AFM微球探针进行定位,在此基础上自动确定AFM探针上的微球针尖与细胞不同部位之间的空间位置关系,进而对细胞中心部位和边缘部位的力学特性进行快速测量。选取HEK 293(人胚胎肾细胞)和HGC-27(人未分化胃癌细胞)两种细胞进行验证实验,并利用Hertz模型对获取的力曲线进行分析以得到细胞杨氏模量。结果在深度学习光学图像自动识别导引下可将AFM探针准确移动至细胞不同部位(中心和边缘)进行力学特性测量,同时实验结果表明,本文提出的方法不仅可对单个游离态细胞进行可靠测量,也适用于聚团生长的细胞。结论深度学习图像识别在辅助AFM单细胞力学特性精准高效探测方面具有巨大潜力,将深度学习图像识别与AFM结合有助于发展面向生物医学应用的高通量单细胞力学特性测量方法。

Atomic force microscopy imaging and mechanical properties measurement of red blood cells and aggressive cancer cells

Mechanical properties play an important role in regulating cellular activities and are critical for unlocking the mysteries of life. Atomic force microscopy (AFM) enables researchers to measure mechanical properties of single living cells under physiological conditions. Here, AFM was used to investigate the topography and mechanical properties of red blood cells (RBCs) and three types of aggressive cancer cells (Burkitt's lymphoma Raji, cutaneous lymphoma Hut, and chronic myeloid leukemia K562). The surface topography of the RBCs and the three cancer cells was mapped with a conventional AFM probe, while mechanical properties were investigated with a microsphere glued onto a tip-less cantilever. The diameters of RBCs are significantly smaller than those of the cancer cells, and mechanical measurements indicated that Young's modulus of RBCs is smaller than those of the cancer cells. Aggressive cancer cells have a lower Young's modulus than that of indolent cancer cells, which may improve our understanding of metastasis.

OPTICALLY TRACKING THE MOTION OF MICROBEADS TO STUDY PHYSICAL BEHAVIORS OF THE LIVING CELL IN RESPONSE TO TRANSIENT STRETCH OR COMPRESSION

Optical magnetic twisting cytometry and traction force microscopy are two advanced cell mechanics research tools that employ optical methods to track the motion of microbeads that are either bound to the surface or embedded in the substrate underneath the cell.The former measures rheological properties of the cell such as cell stiffness,and the latter measures cell traction force dynamics.Here we describe the principles of these two cell mechanics research tools and an example of using them to study physical behaviors of the living cell in response to transient stretch or compression.We demonstrate that,when subjected to a stretch
unstretch manipulation,both the stiffness and traction force of adherent cells promptly reduced,and then gradually recover up to the level prior to the stretch.Immunofluorescent staining and Western blotting results indicate that the actin cytoskeleton of the cells underwent a corresponding disruption and reassembly process almost in step with the changes of cell mechanics.Interestingly,when subjected to compression,the cells did not show such particular behaviors.Taken together,we conclude that adherent cells are very sensitive to the transient stretch but not transient compression,and the stretch-induced cell response is due to the dynamics of actin polymerization.

Unveiling the morphogenetic code:A new path at the intersection of physical energies and chemical signaling

In this editorial,we discuss the remarkable role of physical energies in the control of cell signaling networks and in the specification of the architectural plan of both somatic and stem cells.In particular,we focus on the biological relevance of bioelectricity in the pattern control that orchestrates both developmental and regenerative pathways.To this end,the narrative starts from the dawn of the first studies on animal electricity,reconsidering the pioneer work of Harold Saxton Burr in the light of the current achievements.We finally discuss the most recent evidence showing that bioelectric signaling is an essential component of the informational processes that control pattern specification during embryogenesis,regeneration,or even malignant transformation.We conclude that there is now mounting evidence for the existence of a Morphogenetic Code,and that deciphering this code may lead to unprecedented opportunities for the development of novel paradigms of cure in regenerative and precision medicine.

高血压机械力诱导血管平滑肌细胞结构与功能变化及其在血管疾病中的作用

血压升高产生的机械力在血管分化与发育、血管正常结构与功能维持以及血管病变过程中起决定作用,血脂和/或血糖异常升高可协同机械力作用加速血管重构及疾病发生发展。机械力可非特异性激活血管细胞所有跨膜蛋白分子,引起细胞内多信号通道分子(第二效应分子)同步活化。多通道信号分子在信号网络结点分子汇集,继而再散发,启动更多信号通路活化,实现信号的级联瀑布放大,导致细胞一系列病理生理学变化如细胞分化、迁移、炎症、表型变化、钙化、增殖、凋亡等,最终引起血管的结构与功能改变如动脉粥样硬化等,成为心脑血管疾病致死、致残的主要原因。本文对本课题组及国际同行相关研究进展,亦即血压升高产生的机械力对血管平滑肌细胞作用相关的血管重构做一简要综述。

血管平滑肌细胞中机械力信号受体的研究进展

血管平滑肌细胞(vascular smooth muscle cell,VSMC)在血管生理功能维持和动脉粥样硬化、动脉硬化与钙化、动脉瘤与夹层等血管疾病发生、发展、转归过程中发挥重要作用。因其表型的高度可塑性,VSMC可对血液动力学因素、管壁细胞外基质刚度和拓扑等多种机械力刺激予以应答,通过表型转换而参与血管稳态和重塑调控。本文阐述了VSMC感知、转导和响应其所处力学微环境的关键受体和信号转导途径,并基于作者研究团队近年来的工作,重点介绍了酪氨酸激酶受体型机械力信号受体和核机械力信号受体等在机械力感知过程中的作用和机制。

Changes of Bone Remodeling-related Factors of HPDLF Regulated by Estrogen and Tensile Strain

Estrogen deficiency has been proposed as a risk factor for alveolar bone loss, but whether or not estrogen will influcence the bone rebuilting process during orthodontic tooth movement and what the mechanisms involved remain unclear. The paper aims to provide new information that may elucidate the modulatory effect of estrogen on the bone-resorbing cytokines RANKL and its anti-resorptive factor OPG secrected by HPLFs which are already force-stimulated. The expression of OPG mRNA is rising after mechanical loading either with or without stimulated by estrogen before. But HPDL cells exposured to estrogen for 24 h before loaded tend to express more OPG mRNA. Compared with the no-estrogen group, the inhibit trend of RANKL mRNA is much more apparent in with-estrogen group. Moreover, estrogen and mechanic force time-dependently increased OPG expression and attenuated the RANKL expression.

miR-193a-3p/E2F6调控细胞焦亡在鼻咽癌中的机制研究

目的探讨miR-193a-3p/E2F6在鼻咽癌(NPC)中对细胞焦亡的调控作用及其潜在的分子机制。方法双荧光素酶基因报告实验评估了miR-193a-3p对E2F6的靶向调控作用。HNE-2细胞分为不同处理组:对照组、空白质粒组、沉默E2F6质粒组、空白质粒(miRNA)组、过表达miR-193a-3p组、过表达miRNA+空白(E2F6)质粒组以及过表达miRNA+过表达(E2F6)质粒组。通过qPCR检测miR-193a-3p的表达水平,Western blot检测E2F6蛋白的表达以及NLRP3/Caspase-1/GSDMD/GSDMD-N信号通路的激活情况。同时,使用扫描电子显微镜(scanning electron microscope,SEM)观察细胞形态,CCK-8法评估细胞增殖情况,进行集落形成实验和Transwell实验来检测细胞集落形成数量和迁移数量。结果与对照组(0.90±0.02)和空白质粒组(0.88±0.02)相比,沉默E2F6质粒组中E2F6蛋白(0.26±0.02)的表达水平显著降低,NLRP3/Caspase-1/GSDMD/GSDMD-N信号通路明显被激活,SEM显示细胞发生肿胀。CCK-8实验、集落形成实验和Transwell实验显示细胞活力、集落形成数量和迁移数量均下降(P均<0.05)。双荧光素酶报告基因实验证实E2F6是miR-193a-3p的靶基因。同对照组(1.01±0.03,1.02±0.02)和空白质粒(miRNA)组(1.02±0.04,0.21±0.03)相比,过表达miR-193a-3p组(2.02±0.32,0.23±0.02)中的miR-193a-3p的表达水平升高,E2F6的表达水平显著降低。而NLRP3/Caspase-1/GSDMD/GSDMD-N信号通路明显被激活,SEM显示细胞发生肿胀。CCK-8实验、集落形成实验和Transwell实验显示细胞活力、集落形成数量和迁移数量均下降(P均<0.05)。同过表达miR-193a-3p组和过表达miRNA+空白(E2F6)质粒组相比,发现过表达miR-193a-3p结合过表达E2F6组中E2F6蛋白的含量上升,NLRP3/Caspase-1/GSDMD/GSDMD-N蛋白的含量下降,SEM显示细胞肿胀减轻,CCK-8实验、集落形成实验和Transwell实验显示细胞活力、集落形成数量和迁移数量均上升(P均<0.05)。结论miR-193a-3p通过靶向抑制E2F6激活NLRP3/Caspase-1/GSDMD/GSDMD-N通路,诱导NPC细胞发生细胞焦亡,并抑制其增殖、克隆和侵袭。

推拿治疗骨骼肌损伤的分子生物学机制研究进展

骨骼肌损伤是人们生活中时常发生的一类疾患,严重者可造成肢体活动障碍。推拿治疗骨骼肌损伤类疾病有显著疗效,通过检索近5年来推拿治疗急慢性骨骼肌损伤的相关基础实验文献,对推拿治疗骨骼肌损伤的分子生物学机制研究进展进行总结、归纳,从调控肌卫星细胞、相关生长因子及炎性因子、信号通路、细胞自噬等方面进行综述,以期为临床治疗骨骼肌损伤提供有力的理论依据,并对骨骼肌损伤的研究提供新思路。

结合原子力显微镜和光学图像识别的单细胞力学特性快速测量研究

目的细胞力学特性在生理病理变化过程中起着关键调控作用,开展细胞力学特性研究为揭示生命活动奥秘及疾病发生发展演变规律提供了新的视角。原子力显微镜(AFM)的出现为单细胞力学特性研究提供了强大的技术手段。AFM的独特优势是不需要对活细胞进行任何预处理即可在溶液环境下对天然状态的活细胞力学特性进行高精度(纳米级空间分辨率,皮牛级力感知灵敏度)探测。基于AFM压痕实验的细胞力学特性探测已成为生命科学领域的重要研究方法。然而,现有基于AFM的单细胞力学特性测量主要依赖于人工操作,特别是在测量过程中需要人工控制AFM探针移动到细胞表面特定位置进行压痕实验,导致实验过程耗时费力且效率低下。本文通过将AFM与光学图像自动识别相结合建立了单细胞力学特性快速测量方法。方法分别利用UNet++深度学习网络模型和模板匹配算法识别出光学图像中的细胞及AFM探针,在此基础上自动确定细胞和AFM探针之间的空间位置关系,并控制AFM探针准确移动至目标细胞表面进行压痕实验。在光学显微镜视觉导引下利用AFM微操作将单个微球黏附至AFM探针悬臂梁制作得到球形针尖探针。选取HEK 293(人胚胎肾细胞)和MCF-7(人乳腺癌细胞)两种细胞进行实验。利用Hertz-Sneddon模型对在细胞表面获取的力曲线进行分析得到细胞杨氏模量。结果基于光学图像识别结果可将AFM探针针尖准确移动至目标细胞(HEK 293或MCF-7)并对细胞力学特性进行测量,同时实验结果表明本文所提出的方法不仅适用于常规AFM锥形针尖探针,也适用于AFM球形针尖探针。结论将AFM与光学图像识别结合显著提升了AFM细胞力学特性测量效率,为高通量自动化AFM单细胞力学特性探测提供了新的方法和思路,对于细胞力学特性研究具有广泛的积极意义。

细胞力学2022年度研究进展

细胞的力学微环境在调控其生理功能方面起关键作用。体内细胞经常受到剪切、拉伸、压缩等多种力学载荷,并且可以通过黏附分子(如整合素-配体素的结合)连接到细胞外基质上,进而可以感知外基质的硬度。细胞力学主要研究活细胞在力学载荷下的力学特性和行为,以及这些特征和行为与细胞功能的关系。本文综述2022年度细胞力学领域的研究进展,主要关注整合素-配体素间的相互作用,以及外基质硬度和力学载荷对细胞生理行为和形态发生的影响。