title: Mechanoresponsive, omni-directional and local matrix-degrading actin protrusions in human mesenchymal stem cells microencapsulated in a 3D collagen matrix.
abstract: Cells are known to respond to multiple niche signals including extracellular matrix and mechanical loading. In others and our own studies, mechanical loading has been shown to induce the formation of cell alignment in 3D collagen matrix with random meshwork, challenging our traditional understanding on the necessity of having aligned substrates as the prerequisite of alignment formation. This motivates our adventure in deciphering the mechanism of loading-induced cell alignment and hence the discovery of the novel protrusive functional structure at the cell-matrix interface. Here we report the formation of mechanoresponsive, omni-directional and local matrix-degrading actin protrusions in human mesenchymal stem cells (hMSCs) microencapsulated in collagen following a shifted actin assembly/disassembly balance. These actin protrusive structures exhibit morphological and compositional similarity to filopodia and invadopodia but differ from them in stability, abundance, signaling and function. Without ruling out the possibility that these structures may comprise special subsets of filopodia and invadopodia, we propose to name them as mechanopodia so as to reveal their mechano-inductive mechanism. We also suggest that more intensive investigations are needed to delineate the functional significance and physiological relevance of these structures. This work identifies a brand new target for cell-matrix interaction and mechanoregulation studies.
authors.affiliation: Tissue Engineering Laboratory, Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region.
authors.forename: Fu Chak
authors.initials: FC
authors.lastname: Ho
authors.affiliation: Tissue Engineering Laboratory, Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Tissue Engineering Laboratory, Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region.
authors.forename: Yuk Yin
authors.initials: YY
authors.lastname: Li
authors.affiliation: Tissue Engineering Laboratory, Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region. Electronic address: bpchan@hku.hk.
authors.forename: Barbara Pui
authors.initials: BP
authors.lastname: Chan
mesh_terms: D002478:Cells, Cultured; D003094:Collagen / Q000008:administration & dosage*; D004339:Drug Compounding; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D003094:Collagen; D020764:cdc42 GTP-Binding Protein
keywords: Actin protrusions; Cell–matrix interface; Collagen microencapsulation; Human mesenchymal stem cells; Mechanopodia; Mechanoresponsive