Article ; Online: (with research data) Fragility of foot process morphology in kidney podocytes arises from chaotic spatial propagation of cytoskeletal instability.
2017 Volume 13, Issue 3, Page(s) e1005433
Abstract: ... in regulation of actin bundling lead to chaotic spatial patterns that could impair the foot process morphology ... Kidney podocytes' function depends on fingerlike projections (foot processes) that interdigitate ... regulation of actin dynamics within foot processes controls local morphology. We find that imbalances ...
| Abstract | Kidney podocytes' function depends on fingerlike projections (foot processes) that interdigitate with those from neighboring cells to form the glomerular filtration barrier. The integrity of the barrier depends on spatial control of dynamics of actin cytoskeleton in the foot processes. We determined how imbalances in regulation of actin cytoskeletal dynamics could result in pathological morphology. We obtained 3-D electron microscopy images of podocytes and used quantitative features to build dynamical models to investigate how regulation of actin dynamics within foot processes controls local morphology. We find that imbalances in regulation of actin bundling lead to chaotic spatial patterns that could impair the foot process morphology. Simulation results are consistent with experimental observations for cytoskeletal reconfiguration through dysregulated RhoA or Rac1, and they predict compensatory mechanisms for biochemical stability. We conclude that podocyte morphology, optimized for filtration, is intrinsically fragile, whereby local transient biochemical imbalances may lead to permanent morphological changes associated with pathophysiology. |
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| MeSH term(s) | Actin Cytoskeleton/pathology ; Actin Cytoskeleton/physiology ; Cell Polarity ; Cell Size ; Cell Surface Extensions/pathology ; Cell Surface Extensions/physiology ; Cells, Cultured ; Computer Simulation ; Humans ; Models, Biological ; Nonlinear Dynamics ; Podocytes/pathology ; Podocytes/physiology ; Spatio-Temporal Analysis |
| Language | English |
| Publishing date | 2017-03-16 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural |
| ZDB-ID | 2193340-6 |
| ISSN | 1553-7358 ; 1553-734X |
| ISSN (online) | 1553-7358 |
| ISSN | 1553-734X |
| DOI | 10.1371/journal.pcbi.1005433 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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