Biophysical Regulations of Epigenetic State and Notch Signaling in Neural Development Using Microgroove Substrates

• DOI: 10.1021/acsami.2c01996
• Publication Date: 2022-07-13T18:06:52Z
• Authors: Chia-Chen Hsu; Andrea Serio; Sahana Gopal; Amy Gelmi; Ciro Chiappini; Ravi A. Desai; Molly M. Stevens
• Keywords: 0301 basic medicine; Technology; NEURONAL DIFFERENTIATION; Materials Science; INHIBITION; Materials Science, Multidisciplinary; TOPOGRAPHY; neural tissue engineering; 09 Engineering; neural stem cell; 03 medical and health sciences; topography; VALPROIC ACID; EXTRACELLULAR-MATRIX; CUES; STEM-CELLS DIFFERENTIATION; Nanoscience & Nanotechnology; Notch signaling; Multidisciplinary; Science & Technology; epigenetics; NEURITE GROWTH; STIFFNESS; neuron; micropatterning; 620; Science & Technology - Other Topics; CONTACT GUIDANCE; 03 Chemical Sciences

A number of studies have recently shown how surface topography can alter the behavior and differentiation patterns different types stem cells. Although exact mechanisms molecular pathways involved remain unclear, a consistent portion literature points to epigenetic changes induced by nuclear remodeling. In this study, we investigate clinically relevant neural populations derived from human pluripotent cells when cultured on polydimethylsiloxane microgrooves (3 10 μm depth grooves) what are responsible for their capacity functional behavior. Our results show that enhance cell alignment, modify geometry, significantly increase cellular stiffness, which were able measure at high resolution with combination light electron microscopy, scanning ion conductance microscopy (SICM), atomic force (AFM) coupled quantitative image analysis. The promoted significant in landscape, as revealed expression key histone modification markers. main behavioral change was an neuronal under basal conditions microgrooves. Through measurements cleaved Notch1 levels, found downregulate Notch signaling. We fact propose microgroove affects potential indirectly altering signaling through geometric segregation mechanism parallel topography-dependent modulations acts concert differentiation.