by Keyword: Maturation

Álvarez Z, Ortega JA, Sato K, Sasselli IR, Kolberg-Edelbrock AN, Qiu R, Marshall KA, Nguyen TP, Smith CS, Quinlan KA, Papakis V, Syrgiannis Z, Sather NA, Musumeci C, Engel E, Stupp SI, Kiskinis E, (2023). Artificial extracellular matrix scaffolds of mobile molecules enhance maturation of human stem cell-derived neurons Cell Stem Cell 30, 219-238

Human induced pluripotent stem cell (hiPSC) technologies offer a unique resource for modeling neurological diseases. However, iPSC models are fraught with technical limitations including abnormal aggregation and inefficient maturation of differentiated neurons. These problems are in part due to the absence of synergistic cues of the native extracellular matrix (ECM). We report on the use of three artificial ECMs based on peptide amphiphile (PA) supramolecular nanofibers. All nanofibers display the laminin-derived IKVAV signal on their surface but differ in the nature of their non-bioactive domains. We find that nanofibers with greater intensity of internal supramolecular motion have enhanced bioactivity toward hiPSC-derived motor and cortical neurons. Proteomic, biochemical, and functional assays reveal that highly mobile PA scaffolds caused enhanced β1-integrin pathway activation, reduced aggregation, increased arborization, and matured electrophysiological activity of neurons. Our work highlights the importance of designing biomimetic ECMs to study the development, function, and dysfunction of human neurons.Copyright © 2022 Elsevier Inc. All rights reserved.

JTD Keywords: Dynamics, Extracellular matrix, Ikvav, Ipsc-derived neurons, Laminin, Neuronal maturation, Peptide amphiphiles, Supramolecular motion, Supramolecular nanofibers

Cable, J, Arlotta, P, Parker, KK, Hughes, AJ, Goodwin, K, Mummery, CL, Kamm, RD, Engle, SJ, Tagle, DA, Boj, SF, Stanton, AE, Morishita, Y, Kemp, ML, Norfleet, DA, May, EE, Lu, A, Bashir, R, Feinberg, AW, Hull, SM, Gonzalez, AL, Blatchley, MR, Pulido, NM, Morizane, R, McDevitt, TC, Mishra, D, Mulero-Russe, A, (2022). Engineering multicellular living systems-A Keystone Symposia report Annals Of The New York Academy Of Sciences 1518, 183-195

The ability to engineer complex multicellular systems has enormous potential to inform our understanding of biological processes and disease and alter the drug development process. Engineering living systems to emulate natural processes or to incorporate new functions relies on a detailed understanding of the biochemical, mechanical, and other cues between cells and between cells and their environment that result in the coordinated action of multicellular systems. On April 3-6, 2022, experts in the field met at the Keystone symposium "Engineering Multicellular Living Systems" to discuss recent advances in understanding how cells cooperate within a multicellular system, as well as recent efforts to engineer systems like organ-on-a-chip models, biological robots, and organoids. Given the similarities and common themes, this meeting was held in conjunction with the symposium "Organoids as Tools for Fundamental Discovery and Translation".

JTD Keywords: Brain organoids, Cell diversity, Computational, Dynamics, Engineered living, Engineered organs, Heart, Maturation, Model, Multicellular, Mycobacterium-tuberculosis, Quantitative-analysis, Systems, Tissue deformation

Zambarda C, Pérez González C, Schoenit A, Veits N, Schimmer C, Jung R, Ollech D, Christian J, Roca-Cusachs P, Trepat X, Cavalcanti-Adam EA, (2022). Epithelial cell cluster size affects force distribution in response to EGF-induced collective contractility European Journal Of Cell Biology 101, 151274

Several factors present in the extracellular environment regulate epithelial cell adhesion and dynamics. Among them, growth factors such as EGF, upon binding to their receptors at the cell surface, get internalized and directly activate the acto-myosin machinery. In this study we present the effects of EGF on the contractility of epithelial cancer cell colonies in confined geometry of different sizes. We show that the extent to which EGF triggers contractility scales with the cluster size and thus the number of cells. Moreover, the collective contractility results in a radial distribution of traction forces, which are dependent on integrin β1 peripheral adhesions and transmitted to neighboring cells through adherens junctions. Taken together, EGF-induced contractility acts on the mechanical crosstalk and linkage between the cell-cell and cell-matrix compartments, regulating collective responses.Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.

JTD Keywords: actin, activation, actomyosin, adherens junctions, adhesion, e-cadherin, egf, maturation, mechanical regulation, micropatterning, migration, traction forces, transduction, transmission, Actomyosin, Adherens junctions, Collective contractility, Egf, Epidermal-growth-factor, Micropatterning, Traction forces