title: Heading in the Right Direction: Understanding Cellular Orientation Responses to Complex Biophysical Environments.
abstract: The aim of cardiovascular regeneration is to mimic the biological and mechanical functioning of tissues. For this it is crucial to recapitulate thein vivocellular organization, which is the result of controlled cellular orientation. Cellular orientation response stems from the interaction between the cell and its complex biophysical environment. Environmental biophysical cues are continuously detected and transduced to the nucleus through entwined mechanotransduction pathways. Next to the biochemical cascades invoked by the mechanical stimuli, the structural mechanotransduction pathway made of focal adhesions and the actin cytoskeleton can quickly transduce the biophysical signals directly to the nucleus. Observations linking cellular orientation response to biophysical cues have pointed out that the anisotropy and cyclic straining of the substrate influence cellular orientation. Yet, little is known about the mechanisms governing cellular orientation responses in case of cues applied separately and in combination. This review provides the state-of-the-art knowledge on the structural mechanotransduction pathway of adhesive cells, followed by an overview of the current understanding of cellular orientation responses to substrate anisotropy and uniaxial cyclic strain. Finally, we argue that comprehensive understanding of cellular orientation in complex biophysical environments requires systematic approaches based on the dissection of (sub)cellular responses to the individual cues composing the biophysical niche.
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.|Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
authors.forename: Chiara
authors.initials: C
authors.lastname: Tamiello
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.|Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
authors.forename: Antonetta B C
authors.initials: ABC
authors.lastname: Buskermolen
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.|Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
authors.forename: Frank P T
authors.initials: FPT
authors.lastname: Baaijens
authors.affiliation: Department of Molecular Cell Biology, CARIM School for Cardiovascular Diseases, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Jos L V
authors.initials: JLV
authors.lastname: Broers
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.|Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
authors.forename: Carlijn V C
authors.initials: CVC
authors.lastname: Bouten
keywords: Actin cytoskeleton; Contact guidance; Focal adhesion; Mechanotransduction; Strain avoidance; Structural pathway