Cell Mechanics Drives Migration Modes

2020 ◽  
Vol 15 (01) ◽  
pp. 1-34 ◽  
Author(s):  
Claudia Tanja Mierke
Keyword(s):  
Extracellular Matrix ◽  
Cell Mechanics ◽  
Single Cells ◽  
Biochemical Properties ◽  
Migration And Invasion ◽  
Environmental Cues ◽  
Connective Tissues ◽  
Migration Of Cells

The classical migration modes, such as mesenchymal or amoeboid migration modes, are essentially determined by molecular, morphological or biochemical properties of the cells. These specific properties facilitate the cell migration and invasion through artificial extracellular matrices mimicking the environmental conditions of connective tissues. However, during the migration of cells through narrow extracellular matrix constrictions, the specific extracellular matrix environments can either support or impair the invasion of cells. Beyond the classical molecular or biochemical properties, the migration and invasion of cells depends on intracellular cell mechanical characteristics and extracellular matrix mechanical features. The switch between cell states, such as epithelial, mesenchymal or amoeboid states, seems to be mainly based on epigenetic changes and environmental cues that induce the reversible transition of cells toward another state and thereby promote a specific migration mode. However, the exact number of migration modes is not yet clear. Moreover, it is also unclear whether every individual cell, independent of the type, can undergo a transition between all different migration modes in general. A newer theory states that the transition from the jamming to unjamming phase of clustered cells enables cells to migrate as single cells through extracellular matrix confinements. This review will highlight the mechanical features of cells and their matrix environment that regulate and subsequently determine individual migration modes. It is discussed whether each migration mode in each cell type is detectable or whether some migration modes are limited to artificially engineered matrices in vitro and can therefore not or only rarely be detected in vivo. It is specifically pointed out how the intracellular architecture and its contribution to cellular stiffness or contractility favors the employment of a distinct migration mode. Finally, this review envisions a connection between mechanical properties of cells and matrices and the choice of a distinct migration mode in confined 3D microenvironments.

scholarly journals Functional angiogenesis requires microenvironmental cues balancing endothelial cell migration and proliferation

2019 ◽  
Author(s):  
William Y. Wang ◽  
Daphne Lin ◽  
Evan H. Jarman ◽  
William J. Polacheck ◽  
Brendon M. Baker
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cell ◽  
Single Cells ◽  
Endothelial Cell Migration ◽  
Migration Speed ◽  
Parent Vessel ◽  
Extracellular Milieu ◽  
Cell Functions

ABSTRACTAngiogenesis is a complex morphogenetic process that involves intimate interactions between multicellular endothelial structures and their extracellular milieu. In vitro models of angiogenesis can aid in reducing the complexity of the in vivo microenvironment and provide mechanistic insight into how soluble and physical extracellular matrix cues regulate this process. To investigate how microenvironmental cues regulate angiogenesis and the function of resulting microvasculature, we multiplexed an established angiogenesis-on-a-chip platform that affords higher throughput investigation of 3D endothelial cell sprouting emanating from a parent vessel through defined biochemical gradients and extracellular matrix. We found that two fundamental endothelial cell functions, migration and proliferation, dictate endothelial cell invasion as single cells vs. multicellular sprouts. Microenvironmental cues that elicit excessive migration speed incommensurate with proliferation resulted in microvasculature with poor barrier function and an inability to transport fluid across the microvascular bed. Restoring the balance between migration speed and proliferation rate rescued multicellular sprout invasion, providing a new framework for the design of pro-angiogenic biomaterials that guide functional microvasculature formation for regenerative therapies.

scholarly journals Cell-extracellular matrix interactions in the fluidic phase direct the topology and polarity of self-organized epithelial structures

2020 ◽  
Author(s):  
Mingxing Ouyang ◽  
Jiun-Yann Yu ◽  
Yenyu Chen ◽  
Linhong Deng ◽  
Chin-Lin Guo
Keyword(s):  
Extracellular Matrix ◽  
Large Scale ◽  
Type I Collagen ◽  
Mdck Cells ◽  
Early Stage ◽  
Single Cells ◽  
Confocal Imaging ◽  
Type I

AbstractIn vivo, cells are surrounded by extracellular matrix (ECM). To build organs from single cells, it is generally believed that ECM serves as a large-scale scaffold to coordinate cell positioning and differentiation. Nevertheless, how cells utilize cell-ECM interactions to spatiotemporally coordinate their positioning and differentiation to different ECM at the whole-tissue scale is not fully understood. Here, using in vitro assay with engineered MDCK cells co-expressing H2B-mCherry (nucleus) and gp135 (Podocalyxin)-GFP (apical marker), we show that such spatiotemporal coordination for epithelial morphogenesis and polarization can be initiated and determined by cell-soluble ECM interaction in the fluidic phase. The coordination depends on the native topology of ECM components such as sheet-like basement membrane (BM, mimicked by Matrigel in experiments) and linear fiber-like type I collagen (COL). Two types of coordination are found: scaffold formed by BM (COL) facilitates a close-ended (open-ended) coordination that leads to the formation of lobular (tubular) epithelium, where polarity is preserved throughout the entire lobule/tubule. During lobular formation with BM, polarization of individual cells within the same cluster occurs almost simultaneously, whereas the apicobasal polarization in the presence of COL can start at local regions and proceed in a collective way along the axis of tubule, which might suggest existence of intercellular communications at the cell-population level. Further, in the fluidic phase, we found that cells can form apicobasal polarity throughout the entire lobule/tubule without a complete coverage of ECM at the basal side. Based on reconstructions from time-lapse confocal imaging, this is likely derived from polarization occurring at early stage and being maintained through growth of the epithelial structures. Under suspension culture with COL, the polarization was impaired with formation of multi-lumens on the tubes, implying the importance of ECM microenvironment for tubulogenesis. Our results suggest a mechanism for cells to form polarity and coordinate positioning in vivo, and a strategy for engineering epithelial structures through cell-soluble ECM interaction and self-assembly in vitro.

scholarly journals The role of extracellular matrix in normal and pathological pregnancy: Future applications of microphysiological systems in reproductive medicine

2020 ◽  
Vol 245 (13) ◽  
pp. 1163-1174
Author(s):  
Blakely B O’Connor ◽  
Benjamin D Pope ◽  
Michael M Peters ◽  
Carrie Ris-Stalpers ◽  
Kevin K Parker
Keyword(s):  
Extracellular Matrix ◽  
Cellular Adhesion ◽  
Migration And Invasion ◽  
Matrix Remodeling ◽  
Healthy Pregnancy ◽  
Microphysiological Systems ◽  
Maternal Fetal Interface

Remodeling of extracellular matrix in the womb facilitates the dramatic morphogenesis of maternal and placental tissues necessary to support fetal development. In addition to providing a scaffold to support tissue structure, extracellular matrix influences pregnancy outcomes by facilitating communication between cells and their microenvironment to regulate cellular adhesion, migration, and invasion. By reviewing the functions of extracellular matrix during key developmental milestones, including fertilization, embryo implantation, placental invasion, uterine growth, and labor, we illustrate the importance of extracellular matrix during healthy pregnancy and development. We also discuss how maladaptive matrix expression contributes to infertility and obstetric diseases such as implantation failure, preeclampsia, placenta accreta, and preterm birth. Recently, advances in engineering the biotic–abiotic interface have potentiated the development of microphysiological systems, known as organs-on-chips, to represent human physiological and pathophysiological conditions in vitro. These technologies may offer new opportunities to study human fertility and provide a more granular understanding of the role of adaptive and maladaptive remodeling of the extracellular matrix during pregnancy. Impact statement Extracellular matrix in the womb regulates the initiation, progression, and completion of a healthy pregnancy. The composition and physical properties of extracellular matrix in the uterus and at the maternal–fetal interface are remodeled at each gestational stage, while maladaptive matrix remodeling results in obstetric disease. As in vitro models of uterine and placental tissues, including micro-and milli-scale versions of these organs on chips, are developed to overcome the inherent limitations of studying human development in vivo, we can isolate the influence of cellular and extracellular components in healthy and pathological pregnancies. By understanding and recreating key aspects of the extracellular microenvironment at the maternal–fetal interface, we can engineer microphysiological systems to improve assisted reproduction, obstetric disease treatment, and prenatal drug safety.

scholarly journals The ADAMTS/Fibrillin Connection: Insights into the Biological Functions of ADAMTS10 and ADAMTS17 and Their Respective Sister Proteases

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 596
Author(s):  
Stylianos Z. Karoulias ◽  
Nandaraj Taye ◽  
Sarah Stanley ◽  
Dirk Hubmacher
Keyword(s):  
Extracellular Matrix ◽  
Biochemical Properties ◽  
Biological Functions ◽  
Tissue Development ◽  
Tight Skin ◽  
Human Disorders ◽  
Fibrillin 1 ◽  
Substrate Cleavage

Secreted a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS) proteases play crucial roles in tissue development and homeostasis. The biological and pathological functions of ADAMTS proteases are determined broadly by their respective substrates and their interactions with proteins in the pericellular and extracellular matrix. For some ADAMTS proteases, substrates have been identified and substrate cleavage has been implicated in tissue development and in disease. For other ADAMTS proteases, substrates were discovered in vitro, but the role of these proteases and the consequences of substrate cleavage in vivo remains to be established. Mutations in ADAMTS10 and ADAMTS17 cause Weill–Marchesani syndrome (WMS), a congenital syndromic disorder that affects the musculoskeletal system (short stature, pseudomuscular build, tight skin), the eyes (lens dislocation), and the heart (heart valve abnormalities). WMS can also be caused by mutations in fibrillin-1 (FBN1), which suggests that ADAMTS10 and ADAMTS17 cooperate with fibrillin-1 in a common biological pathway during tissue development and homeostasis. Here, we compare and contrast the biochemical properties of ADAMTS10 and ADAMTS17 and we summarize recent findings indicating potential biological functions in connection with fibrillin microfibrils. We also compare ADAMTS10 and ADAMTS17 with their respective sister proteases, ADAMTS6 and ADAMTS19; both were recently linked to human disorders distinct from WMS. Finally, we propose a model for the interactions and roles of these four ADAMTS proteases in the extracellular matrix.

scholarly journals Design of biomimetic cellular scaffolds for co-culture system and their application

2017 ◽  
Vol 8 ◽  
pp. 204173141772464 ◽  
Author(s):  
Yun-Min Kook ◽  
Yoon Jeong ◽  
Kangwon Lee ◽  
Won-Gun Koh
Keyword(s):  
Extracellular Matrix ◽  
Culture System ◽  
Three Dimensional ◽  
Biochemical Properties ◽  
Culture Systems ◽  
Specific Tissue ◽  
Multicellular Interactions ◽  
Cell Functionality

The extracellular matrix of most natural tissues comprises various types of cells, including fibroblasts, stem cells, and endothelial cells, which communicate with each other directly or indirectly to regulate matrix production and cell functionality. To engineer multicellular interactions in vitro, co-culture systems have achieved tremendous success achieving a more realistic microenvironment of in vivo metabolism than monoculture system in the past several decades. Recently, the fields of tissue engineering and regenerative medicine have primarily focused on three-dimensional co-culture systems using cellular scaffolds, because of their physical and biological relevance to the extracellular matrix of actual tissues. This review discusses several materials and methods to create co-culture systems, including hydrogels, electrospun fibers, microfluidic devices, and patterning for biomimetic co-culture system and their applications for specific tissue regeneration. Consequently, we believe that culture systems with appropriate physical and biochemical properties should be developed, and direct or indirect cell–cell interactions in the remodeled tissue must be considered to obtain an optimal tissue-specific microenvironment.

Desmopressin (DDAVP) Enhances Platelet Adhesion to the Extracellular Matrix of Cultured Human Endothelial Cells through Increased Expression of Tissue Factor

1997 ◽  
Vol 77 (05) ◽  
pp. 0975-0980 ◽  
Author(s):  
Angel Gálvez ◽  
Goretti Gómez-Ortiz ◽  
Maribel Díaz-Ricart ◽  
Ginés Escolar ◽  
Rogelio González-Sarmiento ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Tissue Factor ◽  
Platelet Adhesion ◽  
Umbilical Vein ◽  
Procoagulant Activity ◽  
Experimental Conditions ◽  
Chromogenic Assay

SummaryThe effect of desmopressin (DDAVP) on thrombogenicity, expression of tissue factor and procoagulant activity (PCA) of extracellular matrix (ECM) generated by human umbilical vein endothelial cells cultures (HUVEC), was studied under different experimental conditions. HUVEC were incubated with DDAVP (1, 5 and 30 ng/ml) and then detached from their ECM. The reactivity towards platelets of this ECM was tested in a perfusion system. Coverslips covered with DD A VP-treated ECMs were inserted in a parallel-plate chamber and exposed to normal blood anticoagulated with low molecular weight heparin (Fragmin®, 20 U/ml). Perfusions were run for 5 min at a shear rate of 800 s1. Deposition of platelets on ECMs was significantly increased with respect to control ECMs when DDAVP was used at 5 and 30 ng/ml (p <0.05 and p <0.01 respectively). The increase in platelet deposition was prevented by incubation of ECMs with an antibody against human tissue factor prior to perfusion. Immunofluorescence studies positively detected tissue factor antigen on DDAVP derived ECMs. A chromogenic assay performed under standardized conditions revealed a statistically significant increase in the procoagulant activity of the ECMs produced by ECs incubated with 30 ng/ml DDAVP (p <0.01 vs. control samples). Northern blot analysis revealed increased levels of tissue factor mRNA in extracts from ECs exposed to DDAVP. Our data indicate that DDAVP in vitro enhances platelet adhesion to the ECMs through increased expression of tissue factor. A similar increase in the expression of tissue factor might contribute to the in vivo hemostatic effect of DDAVP.

The Anti-tumor Activity and Mechanisms of rLj-RGD3 on Human Laryngeal Squamous Carcinoma Hep2 Cells

2020 ◽  
Vol 19 (17) ◽  
pp. 2108-2119
Author(s):  
Yang Jin ◽  
Li Lv ◽  
Shu-Xiang Ning ◽  
Ji-Hong Wang ◽  
Rong Xiao
Keyword(s):  
Wound Healing ◽  
Western Blot ◽  
Morphological Changes ◽  
In Vivo Studies ◽  
Migration And Invasion ◽  
Tunel Staining ◽  
Dna Ladder ◽  
Western Blot Assay

Background: Laryngeal Squamous Cell Carcinoma (LSCC) is a malignant epithelial tumor with poor prognosis and its incidence rate increased recently. rLj-RGD3, a recombinant protein cloned from the buccal gland of Lampetra japonica, contains three RGD motifs that could bind to integrins on the tumor cells. Methods: MTT assay was used to detect the inhibitory rate of viability. Giemsa’s staining assay was used to observe the morphological changes of cells. Hoechst 33258 and TUNEL staining assay, DNA ladder assay were used to examine the apoptotic. Western blot assay was applied to detect the change of the integrin signal pathway. Wound-healing assay, migration, and invasion assay were used to detect the mobility of Hep2 cells. H&E staining assay was used to show the arrangement of the Hep2 cells in the solid tumor tissues. Results: In the present study, rLj-RGD3 was shown to inhibit the viability of LSCC Hep2 cells in vitro by inducing apoptosis with an IC50 of 1.23µM. Western blot showed that the apoptosis of Hep2 cells induced by rLj- RGD3 was dependent on the integrin-FAK-Akt pathway. Wound healing, transwells, and western blot assays in vitro showed that rLj-RGD3 suppressed the migration and invasion of Hep2 cells by integrin-FAKpaxillin/ PLC pathway which could also affect the cytoskeleton arrangement in Hep2 cells. In in vivo studies, rLj-RGD3 inhibited the growth, tumor volume, and weight, as well as disturbed the tissue structure of the solid tumors in xenograft models of BALB/c nude mice without reducing their body weights. Conclusion: hese results suggested that rLj-RGD3 is an effective and safe suppressor on the growth and metastasis of LSCC Hep2 cells from both in vitro and in vivo experiments. rLj-RGD3 might be expected to become a novel anti-tumor drug to treat LSCC patients in the near future.

scholarly journals Obesity Potentiates Esophageal Squamous Cell Carcinoma Growth and Invasion by AMPK-YAP Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jia-Huang Liu ◽  
Qi-Fei Wu ◽  
Jun-Ke Fu ◽  
Xiang-Ming Che ◽  
Hai-Jun Li
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Nude Mice ◽  
Serum Glucose ◽  
Migration And Invasion ◽  
Endocrine Effect

Obesity could increase the risk of esophageal squamous cell carcinoma (ESCC) and affect its growth and progression, but the mechanical links are unclear. The objective of the study was to explore the impact of obesity on ESCC growth and progression utilizing in vivo trials and cell experiments in vitro. Diet-induced obese and lean nude mice were inoculated with TE-1 cells, then studied for 4 weeks. Serum glucose, insulin, leptin, and visfatin levels were assayed. Sera of nude mice were obtained and then utilized to culture TE-1. MTT, migration and invasion assays, RT-PCR, and Western blotting were used to analyze endocrine effect of obesity on cell proliferation, migration, invasion, and related genes expression of TE-1. Obese nude mice bore larger tumor xenografts than lean animals, and were hyperglycemic and hyperinsulinemic with an elevated level of leptin and visfatin in sera, and also were accompanied by a fatty liver. As for the subcutaneous tumor xenograft model, tumors were more aggressive in obese nude mice than lean animals. Tumor weight correlated positively with mouse body weight, liver weight of mice, serum glucose, HOMA-IR, leptin, and visfatin. Obesity prompted significant TE-1 cell proliferation, migration, and invasion by endocrine mechanisms and impacted target genes. The expression of AMPK and p-AMPK protein decreased significantly ( P < 0.05 ); MMP9, total YAP, p-YAP, and nonphosphorylated YAP protein increased significantly ( P < 0.05 ) in the cells cultured with conditioned media and xenograft tumor from the obese group; the mRNA expression of AMPK decreased significantly ( P < 0.05 ); YAP and MMP9 mRNA expression increased significantly ( P < 0.05 ) in the cells exposed to conditioned media from the obese group. In conclusion, the altered adipokine milieu and metabolites in the context of obesity may promote ESCC growth in vivo; affect proliferation, migration, and invasion of ESCC cells in vitro; and regulate MMP9 and AMPK-YAP signaling pathway through complex effects including the endocrine effect.

scholarly journals HDAC4 promotes nasopharyngeal carcinoma progression and serves as a therapeutic target

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Chun Cheng ◽  
Jun Yang ◽  
Si-Wei Li ◽  
Guofu Huang ◽  
Chenxi Li ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Tumor Growth ◽  
Therapeutic Target ◽  
Histone Deacetylases ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
E Cadherin

AbstractHistone deacetylases (HDACs) are involved in tumor progression, and some have been successfully targeted for cancer therapy. The expression of histone deacetylase 4 (HDAC4), a class IIa HDAC, was upregulated in our previous microarray screen. However, the role of HDAC4 dysregulation and mechanisms underlying tumor growth and metastasis in nasopharyngeal carcinoma (NPC) remain elusive. Here, we first confirmed that the HDAC4 levels in primary and metastatic NPC tissues were significantly increased compared with those in normal nasopharyngeal epithelial tissues and found that high HDAC4 expression predicted a poor overall survival (OS) and progression-free survival (PFS). Functionally, HDAC4 accelerated cell cycle G1/S transition and induced the epithelial-to-mesenchymal transition to promote NPC cell proliferation, migration, and invasion in vitro, as well as tumor growth and lung metastasis in vivo. Intriguingly, knockdown of N-CoR abolished the effects of HDAC4 on the invasion and migration abilities of NPC cells. Mechanistically, HDAC3/4 binds to the E-cadherin promoter to repress E-cadherin transcription. We also showed that the HDAC4 inhibitor tasquinimod suppresses tumor growth in NPC. Thus, HDAC4 may be a potential diagnostic marker and therapeutic target in patients with NPC.

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