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Britta Trappmann

Bio: Britta Trappmann is an academic researcher from Max Planck Society. The author has contributed to research in topics: Extracellular matrix & Medicine. The author has an hindex of 19, co-authored 32 publications receiving 3256 citations. Previous affiliations of Britta Trappmann include Harvard University & University of Pennsylvania.

Papers
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Journal ArticleDOI
TL;DR: It is concluded that stem cells exert a mechanical force on collagen fibres and gauge the feedback to make cell-fate decisions, and are regulated by the elastic modulus of PAAm.
Abstract: To investigate how substrate properties influence stem-cell fate, we cultured single human epidermal stem cells on polydimethylsiloxane (PDMS) and polyacrylamide (PAAm) hydrogel surfaces, 0.1 kPa-2.3 MPa in stiffness, with a covalently attached collagen coating. Cell spreading and differentiation were unaffected by polydimethylsiloxane stiffness. However, cells on polyacrylamide of low elastic modulus (0.5 kPa) could not form stable focal adhesions and differentiated as a result of decreased activation of the extracellular-signal-related kinase (ERK)/mitogen-activated protein kinase (MAPK) signalling pathway. The differentiation of human mesenchymal stem cells was also unaffected by PDMS stiffness but regulated by the elastic modulus of PAAm. Dextran penetration measurements indicated that polyacrylamide substrates of low elastic modulus were more porous than stiff substrates, suggesting that the collagen anchoring points would be further apart. We then changed collagen crosslink concentration and used hydrogel-nanoparticle substrates to vary anchoring distance at constant substrate stiffness. Lower collagen anchoring density resulted in increased differentiation. We conclude that stem cells exert a mechanical force on collagen fibres and gauge the feedback to make cell-fate decisions.

1,393 citations

Journal ArticleDOI
TL;DR: A departure from the well-described relationship between material stiffness and spreading established with hydrogel surfaces is demonstrated, and fiber recruitment is introduced as a novel mechanism by which cells probe and respond to mechanics in fibrillar matrices.
Abstract: To investigate how cells sense stiffness in settings structurally similar to native extracellular matrices, we designed a synthetic fibrous material with tunable mechanics and user-defined architecture. In contrast to flat hydrogel surfaces, these fibrous materials recapitulated cell-matrix interactions observed with collagen matrices including stellate cell morphologies, cell-mediated realignment of fibres, and bulk contraction of the material. Increasing the stiffness of flat hydrogel surfaces induced mesenchymal stem cell spreading and proliferation; however, increasing fibre stiffness instead suppressed spreading and proliferation for certain network architectures. Lower fibre stiffness permitted active cellular forces to recruit nearby fibres, dynamically increasing ligand density at the cell surface and promoting the formation of focal adhesions and related signalling. These studies demonstrate a departure from the well-described relationship between material stiffness and spreading established with hydrogel surfaces, and introduce fibre recruitment as a previously undescribed mechanism by which cells probe and respond to mechanics in fibrillar matrices.

452 citations

Journal ArticleDOI
TL;DR: Micropatterned surfaces are employed to identify the signalling pathways by which restricted ECM contact triggers human epidermal stem cells to initiate terminal differentiation and demonstrate how biophysical cues are transduced into transcriptional responses that determine epidersmal cell fate.
Abstract: How cell shape influences cell fate decisions is unclear. Epidermal stem cell fate is regulated by cell shape through the actin cytoskeleton and SRF transcriptional activity.

416 citations

Journal ArticleDOI
TL;DR: An in vitro model whereby molded tubular channels inside a synthetic hydrogel are seeded with endothelial cells and subjected to chemokine gradients within a microfluidic device is developed and it is found that matrix degradability modulates the collectivity of cell migration.
Abstract: A major challenge in tissue engineering is the development of materials that can support angiogenesis, wherein endothelial cells from existing vasculature invade the surrounding matrix to form new vascular structures. To identify material properties that impact angiogenesis, here we have developed an in vitro model whereby molded tubular channels inside a synthetic hydrogel are seeded with endothelial cells and subjected to chemokine gradients within a microfluidic device. To accomplish precision molding of hydrogels and successful integration with microfluidics, we developed a class of hydrogels that could be macromolded and micromolded with high shape and size fidelity by eliminating swelling after polymerization. Using this material, we demonstrate that matrix degradability switches three-dimensional endothelial cell invasion between two distinct modes: single-cell migration and the multicellular, strand-like invasion required for angiogenesis. The ability to incorporate these tunable hydrogels into geometrically constrained settings will enable a wide range of previously inaccessible biomedical applications. The fabrication of vascularized 3D tissues requires an understanding of how material properties govern endothelial cell invasion into the surrounding matrix. Here the authors integrate a non-swelling synthetic hydrogel with a microfluidic device to study chemokine gradient-driven angiogenic sprouting and find that matrix degradability modulates the collectivity of cell migration.

182 citations

Journal ArticleDOI
TL;DR: This perspective examines the ways in which new materials are being used to advance the understanding of how ECM stiffness impacts cell function.

177 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: A microfluidic cell culture device created with microchip manufacturing methods that contains continuously perfused chambers inhabited by living cells arranged to simulate tissue- and organ-level physiology has great potential to advance the study of tissue development, organ physiology and disease etiology.
Abstract: Organ-level physiology is recapitulated in vitro by culturing cells in perfused, microfluidic devices.

2,339 citations

Journal ArticleDOI
30 Aug 2013-Science
TL;DR: In this article, proteomics analyses revealed that levels of the nucleoskeletal protein lamin-A scaled with tissue elasticity, as did levels of collagens in the extracellular matrix that determine E.
Abstract: Tissues can be soft like fat, which bears little stress, or stiff like bone, which sustains high stress, but whether there is a systematic relationship between tissue mechanics and differentiation is unknown. Here, proteomics analyses revealed that levels of the nucleoskeletal protein lamin-A scaled with tissue elasticity, E, as did levels of collagens in the extracellular matrix that determine E. Stem cell differentiation into fat on soft matrix was enhanced by low lamin-A levels, whereas differentiation into bone on stiff matrix was enhanced by high lamin-A levels. Matrix stiffness directly influenced lamin-A protein levels, and, although lamin-A transcription was regulated by the vitamin A/retinoic acid (RA) pathway with broad roles in development, nuclear entry of RA receptors was modulated by lamin-A protein. Tissue stiffness and stress thus increase lamin-A levels, which stabilize the nucleus while also contributing to lineage determination.

1,563 citations

Journal ArticleDOI
TL;DR: This data indicates that self-Assembled Monolayers and Walled Carbon Nanotubes with high adhesion to Nitroxide-Mediated Polymerization have potential in the well-Defined Polymer Age.
Abstract: Keywords: Fragmentation Chain-Transfer ; Self-Assembled Monolayers ; Walled Carbon Nanotubes ; Well-Defined Polymer ; Nitroxide-Mediated Polymerization ; Block-Copolymer Brushes ; Poly(Methyl Methacrylate) Brushes ; Transfer Raft Polymerization ; Quartz-Crystal Microbalance ; Poly(Acrylic Acid) Brushes Reference EPFL-REVIEW-148464doi:10.1021/cr900045aView record in Web of Science Record created on 2010-04-23, modified on 2017-05-10

1,542 citations

Journal ArticleDOI
TL;DR: Progress towards understanding the molecular, cellular and tissue-level effects that promote mechanical homeostasis has helped to identify key questions for future research.
Abstract: Soft connective tissues at steady state are dynamic; resident cells continually read environmental cues and respond to them to promote homeostasis, including maintenance of the mechanical properties of the extracellular matrix (ECM) that are fundamental to cellular and tissue health. The mechanosensing process involves assessment of the mechanics of the ECM by the cells through integrins and the actomyosin cytoskeleton, and is followed by a mechanoregulation process, which includes the deposition, rearrangement or removal of the ECM to maintain overall form and function. Progress towards understanding the molecular, cellular and tissue-level effects that promote mechanical homeostasis has helped to identify key questions for future research.

1,449 citations