Schaumann, E. N. | bioRxiv Science

bioRxiv2019

Silicon Nanowires for Intracellular Optical Interrogation with Sub-Cellular Resolution

Current techniques for intracellular electrical interrogation are substrate bound and are technically demanding, or lack high spatial resolution. In this work, we use silicon nanowires, which are spontaneously internalized by many cell types, to achieve photo-stimulation with sub-cellular resolution. Myofibroblasts loaded with silicon nanowires remain viable and can undergo cell division. Stimulation of silicon nanowires at separate intracellular locations results in local calcium fluxes. We also show that nanowire-containing myofibroblasts can electrically couple to cardiomyocytes in co-culture and that photo-stimulation of the nanowires increases the spontaneous activation rate in neighboring cardiomyocytes. Finally, we demonstrate that this methodology can be extended to the interrogation of signaling in neuron-glia interactions using nanowire-containing oligodendrocytes.

bioengineering↗

bioRxiv2018

Force localization modes in dynamic epithelial colonies

Collective cell behaviors, including tissue remodeling, morphogenesis and cancer metastasis rely on dynamics between cells, their neighbors and the extracellular matrix. The lack of quantitative models precludes understanding of how cell-cell and cell-matrix interactions regulate tissue-scale force transmission to guide morphogenic processes. We integrate biophysical measurements on model epithelial tissues and computational modelling to explore how cell-level dynamics alter mechanical stress organization at multicellular scales. We show that traction stress distribution in epithelial colonies can vary widely for identical geometries. For colonies with peripheral localization of traction stresses, we recapitulate previously described mechanical behavior of cohesive tissues with a continuum model. By contrast, highly motile cells within colonies produce traction stresses that fluctuate in space and time. To predict the traction force dynamics, we introduce an Active Adherent Vertex Model (AAVM) for epithelial monolayers. AAVM predicts that increased cellular motility and reduced intercellular mechanical coupling localize traction stresses in the colony interior, in agreement with our experimental data. Furthermore, the model captures a wide spectrum of localized stress production modes that arise from individual cell activities including cell division, rotation, and polarized migration. This approach provides a robust quantitative framework to study how cell-scale dynamics influence force transmission in epithelial tissues.

biophysics↗