title: New concepts in basement membrane biology.
abstract: Basement membranes (BMs) are thin sheets of extracellular matrix that outline epithelia, muscle fibers, blood vessels and peripheral nerves. The current view of BM structure and functions is based mainly on transmission electron microscopy imaging, in vitro protein binding assays, and phenotype analysis of human patients, mutant mice and invertebrata. Recently, MS-based protein analysis, biomechanical testing and cell adhesion assays with in vivo derived BMs have led to new and unexpected insights. Proteomic analysis combined with ultrastructural studies showed that many BMs undergo compositional and structural changes with advancing age. Atomic force microscopy measurements in combination with phenotype analysis have revealed an altered mechanical stiffness that correlates with specific BM pathologies in mutant mice and human patients. Atomic force microscopy-based height measurements strongly suggest that BMs are more than two-fold thicker than previously estimated, providing greater freedom for modelling the large protein polymers within BMs. In addition, data gathered using BMs extracted from mutant mice showed that laminin has a crucial role in BM stability. Finally, recent evidence demonstrate that BMs are bi-functionally organized, leading to the proposition that BM-sidedness contributes to the alternating epithelial and stromal tissue arrangements that are found in all metazoan species. We propose that BMs are ancient structures with tissue-organizing functions and were essential in the evolution of metazoan species.
authors: Department of Ophthalmology, University Hospital Basel, Switzerland.
authors: Willi
authors: W
authors: Halfter
authors: Biozentrum and the Swiss Nanoscience Institute, University of Basel, Switzerland.
authors: Philipp
authors: P
authors: Oertle
authors: Biozentrum and the Swiss Nanoscience Institute, University of Basel, Switzerland.
authors: Christophe A
authors: CA
authors: Monnier
authors: Biozentrum and the Swiss Nanoscience Institute, University of Basel, Switzerland.
authors: Leon
authors: L
authors: Camenzind
authors: Department of Ophthalmology, University Hospital Basel, Switzerland.
authors: Magaly
authors: M
authors: Reyes-Lua
authors: Department of Neurobiology and Physiology, Upstate University Hospital, SUNY University, Syracuse, NY, USA.
authors: Huaiyu
authors: H
authors: Hu
authors: Department of Bioengeneering, University of Pittsburgh, PA, USA.
authors: Joseph
authors: J
authors: Candiello
authors: Department of Renal Physiology, University of Pittsburgh, PA, USA.
authors: Anatalia
authors: A
authors: Labilloy
authors: Proteomics Core Facility of the University of Pittsburgh, PA, USA.
authors: Manimalha
authors: M
authors: Balasubramani
authors: Department of Ophthalmology, University Hospital Basel, Switzerland.
authors: Paul Bernhard
authors: PB
authors: Henrich
authors: Biozentrum and the Swiss Nanoscience Institute, University of Basel, Switzerland.|Department of Pathology, University Hospital Basel, Switzerland.
authors: Marija
authors: M
authors: Plodinec
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D018625:Microscopy, Atomic Force; D040901:Proteomics
keywords: basal lamina; basement membrane; biomechanical properties; collagen IV; laminin; membrane asymmetry; nidogen; perlecan