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Title: The microstructure of laminin-111 compensates for dystroglycan loss in mammary epithelial cells in downstream expression of milk proteins

Abstract

Laminin-111 (Ln-1), an extracellular matrix (ECM) glycoprotein found in the basement membrane of mammary gland epithelia, is essential for lactation. In mammary epithelial cells (MECs), dystroglycan (Dg) is believed to be necessary for polymerization of laminin-111 into networks., thus we asked whether correct polymerization could compensate for Dg loss. Artificially polymerized laminin-111 and the laminin-glycoprotein mix Matrigel, both formed branching, spread networks with fractal dimensions from 1.7 to 1.8, whereas laminin-111 in neutral buffers formed small aggregates without fractal properties (a fractal dimension of 2). In Dg knockout cells, either polymerized laminin-111 or Matrigel readily attached to the cell surface, whereas aggregated laminin-111 did not. In contrast, polymerized and aggregated laminin-111 bound similarly to Dg knock-ins. Both polymerized laminin-111 and Matrigel promoted cell rounding, clustering, formation of tight junctions, and expression of milk proteins, whereas aggregated Ln-1 did not attach to cells or promote functional differentiation. Finally, these findings support that the microstructure of Ln-1 networks in the basement membrane regulates mammary epithelial cell function.

Authors:
 [1];  [1];  [1];  [2];  [1];  [3]
  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  2. Texas Heart Inst., Houston, TX (United States)
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1760179
Alternate Identifier(s):
OSTI ID: 1564332
Report Number(s):
LLNL-JRNL-766544
Journal ID: ISSN 0142-9612; ark:/13030/qt44v5c2wx
Grant/Contract Number:  
AC02-05CH11231; AC52-07NA27344; BC133875; LDRD 18-ERD-062; NIH R01CA064786
Resource Type:
Accepted Manuscript
Journal Name:
Biomaterials
Additional Journal Information:
Journal Volume: 218; Journal ID: ISSN 0142-9612
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; laminin; dystroglycan; microstructure; mammary differentiation

Citation Formats

Kent, A. J., Mayer, N., Inman, J. L., Hochman-Mendez, C., Bissell, M. J., and Robertson, C. The microstructure of laminin-111 compensates for dystroglycan loss in mammary epithelial cells in downstream expression of milk proteins. United States: N. p., 2019. Web. doi:10.1016/j.biomaterials.2019.119337.
Kent, A. J., Mayer, N., Inman, J. L., Hochman-Mendez, C., Bissell, M. J., & Robertson, C. The microstructure of laminin-111 compensates for dystroglycan loss in mammary epithelial cells in downstream expression of milk proteins. United States. doi:https://doi.org/10.1016/j.biomaterials.2019.119337
Kent, A. J., Mayer, N., Inman, J. L., Hochman-Mendez, C., Bissell, M. J., and Robertson, C. Tue . "The microstructure of laminin-111 compensates for dystroglycan loss in mammary epithelial cells in downstream expression of milk proteins". United States. doi:https://doi.org/10.1016/j.biomaterials.2019.119337. https://www.osti.gov/servlets/purl/1760179.
@article{osti_1760179,
title = {The microstructure of laminin-111 compensates for dystroglycan loss in mammary epithelial cells in downstream expression of milk proteins},
author = {Kent, A. J. and Mayer, N. and Inman, J. L. and Hochman-Mendez, C. and Bissell, M. J. and Robertson, C.},
abstractNote = {Laminin-111 (Ln-1), an extracellular matrix (ECM) glycoprotein found in the basement membrane of mammary gland epithelia, is essential for lactation. In mammary epithelial cells (MECs), dystroglycan (Dg) is believed to be necessary for polymerization of laminin-111 into networks., thus we asked whether correct polymerization could compensate for Dg loss. Artificially polymerized laminin-111 and the laminin-glycoprotein mix Matrigel, both formed branching, spread networks with fractal dimensions from 1.7 to 1.8, whereas laminin-111 in neutral buffers formed small aggregates without fractal properties (a fractal dimension of 2). In Dg knockout cells, either polymerized laminin-111 or Matrigel readily attached to the cell surface, whereas aggregated laminin-111 did not. In contrast, polymerized and aggregated laminin-111 bound similarly to Dg knock-ins. Both polymerized laminin-111 and Matrigel promoted cell rounding, clustering, formation of tight junctions, and expression of milk proteins, whereas aggregated Ln-1 did not attach to cells or promote functional differentiation. Finally, these findings support that the microstructure of Ln-1 networks in the basement membrane regulates mammary epithelial cell function.},
doi = {10.1016/j.biomaterials.2019.119337},
journal = {Biomaterials},
number = ,
volume = 218,
place = {United States},
year = {2019},
month = {7}
}

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