7 research outputs found
Cell-geometry-dependent changes in plasma membrane order direct stem cell signalling and fate
Cell size and shape affect cellular processes such as cell survival, growth and differentiation1,2,3,4, thus establishing cell geometry as a fundamental regulator of cell physiology. The contributions of the cytoskeleton, specifically actomyosin tension, to these effects have been described, but the exact biophysical mechanisms that translate changes in cell geometry to changes in cell behaviour remain mostly unresolved. Using a variety of innovative materials techniques, we demonstrate that the nanostructure and lipid assembly within the cell plasma membrane are regulated by cell geometry in a ligand-independent manner. These biophysical changes trigger signalling events involving the serine/threonine kinase Akt/protein kinase B (PKB) that direct cell-geometry-dependent mesenchymal stem cell differentiation. Our study defines a central regulatory role by plasma membrane ordered lipid raft microdomains in modulating stem cell differentiation with potential translational applications
In vivo biomolecular imaging of zebrafish embryos using confocal Raman spectroscopy
Zebrafish embryos provide a unique opportunity to visualize complex biological processes, yet conventional imaging modalities are unable to access intricate biomolecular information without compromising the integrity of the embryos. Here, we report the use of confocal Raman spectroscopic imaging for the visualization and multivariate analysis of biomolecular information extracted from unlabeled zebrafish embryos. We outline broad applications of this method in: (i) visualizing the biomolecular distribution of whole embryos in three dimensions, (ii) resolving anatomical features at subcellular spatial resolution, (iii) biomolecular profiling and discrimination of wild type and ΔRD1 mutant Mycobacterium marinum strains in a zebrafish embryo model of tuberculosis and (iv) in vivo temporal monitoring of the wound response in living zebrafish embryos. Overall, this study demonstrates the application of confocal Raman spectroscopic imaging for the comparative bimolecular analysis of fully intact and living zebrafish embryos
Cell-geometry-dependent changes in plasma membrane order direct stem cell signalling and fate
Control of fibroblast shape in sequentially formed 3D hybrid hydrogels regulates cellular responses to microenvironmental cues
An integrated enhancement and reconstruction strategy for the quantitative extraction of actin stress fibers from fluorescence micrographs
Advancing Cell-Instructive Biomaterials Through Increased Understanding of Cell Receptor Spacing and Material Surface Functionalization
The stiffness of living tissues and its implications for tissue engineering
The past 20 years have witnessed ever- growing evidence that the mechanical
properties of biological tissues, from nanoscale to macroscale dimensions, are fundamental
for cellular behaviour and consequent tissue functionality. This knowledge, combined with
previously known biochemical cues, has greatly advanced the field of biomaterial development,
tissue engineering and regenerative medicine. It is now established that approaches to engineer
biological tissues must integrate and approximate the mechanics, both static and dynamic,
of native tissues. Nevertheless, the literature on the mechanical properties of biological tissues
differs greatly in methodology, and the available data are widely dispersed. This Review gathers
together the most important data on the stiffness of living tissues and discusses the intricacies
of tissue stiffness from a materials perspective, highlighting the main challenges associated
with engineering lifelike tissues and proposing a unified view of this as yet unreported topic.
Emerging advances that might pave the way for the next decadeâ s take on bioengineered tissue
stiffness are also presented, and differences and similarities between tissues in health and disease
are discussed, along with various techniques for characterizing tissue stiffness at various
dimensions from individual cells to organs.The authors would like to acknowledge financial support from the European Research
Council, grant agreement ERC-2012-ADG 20120216-321266 (project ComplexiTE).
C.F.G. acknowledges scholarship grant no. PD/BD/135253/2017 from Fundação para a
Ciência e Tecnologia (FCT). The authors also thank the peer-reviewers for the
constructive comments and suggestions that helped to shape this manuscript