Extracellular matrix determinants of cell migration mode

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Micropatterned ECM screening array for studying how adhesive cues regulate fibroblast migration.  

Cell migration plays an essential role in development, tissue homeostasis, and cancer metastasis. Although historically studied on flat rigid surfaces, it is now appreciated that within tissues, ECM structure and mechanics critically define a diversity of cell migration strategies and underlying mechanisms. To better understand how physical properties of the ECM influence cell migration, our group integrates microfabricated devices with synthetic biomaterials to create 3D fibrous microenvironments that recapitulate physiologic settings while enabling mechanistic studies. With the use of 3D timelapse imaging and molecular reporters, we employ these in vitro platforms in studying how (1) collective endothelial cell sprouting is orchestrated during angiogenesis, (2) fibroblasts are recruited to fibrotic tissues or wound sites, and (3) cancer cells disseminate through fibrillar tumor stroma in order to metastasize.

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We study single mesenchymal cell migration through fibrous matrices and multicellular migration during angiogenesis.

Trainees:  William Wang, Harrison Hiraki, Daniel Matera
 
Collaborators:  Carole Parent 
Relevant recent publications:
The Role of Rho GTPases During Fibroblast Spreading, Migration, and Myofibroblast Differentiation in 3D Synthetic Fibrous Matrices
Matera DL, Lee AT, Hiraki HL, Baker BM.
Cellular and Molecular Bioengineering. 2021 Sep 2;14(5):381-396. PMID: 34777599; PMCID: PMC8548490.
Direct comparison of angiogenesis in natural and synthetic biomaterials reveals that matrix porosity regulates endothelial cell invasion speed and sprout diameter
Wang WY, Kent RN, Huang SA, Jarman EH, Shikanov EH, Davidson CD, Hiraki HL, Lin D, Wall MA, Matera DL, Shin JW, Polacheck WJ, Shikanov A, Baker BM.
Acta Biomaterialia. 2021 Aug 29:S1742-7061(21)00571-7. PMID: 34469789.
Magnetic alignment of electrospun fiber segments within a hydrogel composite guides cell spreading and migration phenotype switching
Hiraki HL, Matera DL, Rose MJ, Kent RN, Todd CW, Stout ME, Wank AE, Schiavone MC, DePalma SD, Zarouk AA, Baker BM.
Frontiers in Bioengineering and Biotechnology. 2021 Jun 16;9:679165. PMID: 34222216; PMCID: PMC8242362.
Dynamic endothelial stalk cell-matrix interactions regulate angiogenic sprout diameter
Wang WY, Jarman EH, Lin D, Baker BM.
Frontiers in Bioengineering and Biotechnology. 2021 Mar 19;9:620128. PMID: 33869150; PMCID: PMC8044977.
 
Functional angiogenesis requires microenvironmental cues balancing endothelial cell migration and proliferation
Wang WY, Lin D, Jarman EH, Polacheck WJ, Baker BM.
Lab on a Chip, 2020, 20: 1153-1166.
Actomyosin contractility-dependent matrix stretch and recoil induces rapid cell migration
Wang WY, Davidson CD, Lin D, Baker BM.
Nature Communications, 2019, 10(1):1186.
 
Extracellular matrix alignment dictates the organization of focal adhesions and directs uniaxial cell migration

Wang WY, Pearson AT, Kutys ML, Choi CK, Wozniak MA, Baker BM, Chen CS.
APL Bioengineering, 2018, 2(4):046107.

 

Matrix degradability controls multicellularity of 3D cell migration 
Trappmann B*, Baker BM*, Polacheck WJ, Choi CK, Burdick JA, Chen CS.  * authors contributed equally. .
Nature Communications, 2017, 8(1):371.