Synergistic regulation of cerebellar Purkinje neuron development by laminin epitopes and collagen on an artificial hybrid matrix construct

Shantanu Sur, Mustafa O. Guler, Matthew J. Webber, Eugene T. Pashuck, Masao Ito, Samuel I Stupp, Thomas Launey

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The extracellular matrix (ECM) creates a dynamic environment around the cells in the developing central nervous system, providing them with the necessary biochemical and biophysical signals. Although the functions of many ECM molecules in neuronal development have been individually studied in detail, the combinatorial effects of multiple ECM components are not well characterized. Here we demonstrate that the expression of collagen and laminin-1 (lam-1) are spatially and temporally correlated during embryonic and post-natal development of the cerebellum. These changes in ECM distribution correspond to specific stages of Purkinje neuron (PC) migration, somatic monolayer formation and polarization. To clarify the respective roles of these ECM molecules on PC development, we cultured cerebellar neurons on a hybrid matrix comprised of collagen and a synthetic peptide amphiphile nanofiber bearing a potent lam-1 derived bioactive IKVAV peptide epitope. By systematically varying the concentration and ratio of collagen and the laminin epitope in the matrix, we could demonstrate a synergistic relationship between these two ECM components in controlling multiple aspects of PC maturation. An optimal ratio of collagen and IKVAV in the matrix was found to promote maximal PC survival and dendrite growth, while dendrite penetration into the matrix was enhanced by a high IKVAV to collagen ratio. In addition, the laminin epitope was found to guide PC axon development. By combining our observations in vivo and in vitro, we propose a model of PC development where the synergistic effects of collagen and lam-1 play a key role in migration, polarization and morphological maturation of PCs. This journal is

Original languageEnglish
Pages (from-to)903-914
Number of pages12
JournalBiomaterials Science
Volume2
Issue number6
DOIs
Publication statusPublished - 2014

Fingerprint

Epitopes
Laminin
Collagen
Neurons
isoleucyl-lysyl-valyl-alanyl-valine
Peptides
Bearings (structural)
Polarization
Amphiphiles
Molecules
Neurology
Nanofibers
Monolayers

ASJC Scopus subject areas

  • Materials Science(all)
  • Biomedical Engineering

Cite this

Synergistic regulation of cerebellar Purkinje neuron development by laminin epitopes and collagen on an artificial hybrid matrix construct. / Sur, Shantanu; Guler, Mustafa O.; Webber, Matthew J.; Pashuck, Eugene T.; Ito, Masao; Stupp, Samuel I; Launey, Thomas.

In: Biomaterials Science, Vol. 2, No. 6, 2014, p. 903-914.

Research output: Contribution to journalArticle

Sur, Shantanu ; Guler, Mustafa O. ; Webber, Matthew J. ; Pashuck, Eugene T. ; Ito, Masao ; Stupp, Samuel I ; Launey, Thomas. / Synergistic regulation of cerebellar Purkinje neuron development by laminin epitopes and collagen on an artificial hybrid matrix construct. In: Biomaterials Science. 2014 ; Vol. 2, No. 6. pp. 903-914.
@article{b59fe2048a5f4a87b596f9eefce6b278,
title = "Synergistic regulation of cerebellar Purkinje neuron development by laminin epitopes and collagen on an artificial hybrid matrix construct",
abstract = "The extracellular matrix (ECM) creates a dynamic environment around the cells in the developing central nervous system, providing them with the necessary biochemical and biophysical signals. Although the functions of many ECM molecules in neuronal development have been individually studied in detail, the combinatorial effects of multiple ECM components are not well characterized. Here we demonstrate that the expression of collagen and laminin-1 (lam-1) are spatially and temporally correlated during embryonic and post-natal development of the cerebellum. These changes in ECM distribution correspond to specific stages of Purkinje neuron (PC) migration, somatic monolayer formation and polarization. To clarify the respective roles of these ECM molecules on PC development, we cultured cerebellar neurons on a hybrid matrix comprised of collagen and a synthetic peptide amphiphile nanofiber bearing a potent lam-1 derived bioactive IKVAV peptide epitope. By systematically varying the concentration and ratio of collagen and the laminin epitope in the matrix, we could demonstrate a synergistic relationship between these two ECM components in controlling multiple aspects of PC maturation. An optimal ratio of collagen and IKVAV in the matrix was found to promote maximal PC survival and dendrite growth, while dendrite penetration into the matrix was enhanced by a high IKVAV to collagen ratio. In addition, the laminin epitope was found to guide PC axon development. By combining our observations in vivo and in vitro, we propose a model of PC development where the synergistic effects of collagen and lam-1 play a key role in migration, polarization and morphological maturation of PCs. This journal is",
author = "Shantanu Sur and Guler, {Mustafa O.} and Webber, {Matthew J.} and Pashuck, {Eugene T.} and Masao Ito and Stupp, {Samuel I} and Thomas Launey",
year = "2014",
doi = "10.1039/c3bm60228a",
language = "English",
volume = "2",
pages = "903--914",
journal = "Biomaterials Science",
issn = "2047-4830",
publisher = "Royal Society of Chemistry",
number = "6",

}

TY - JOUR

T1 - Synergistic regulation of cerebellar Purkinje neuron development by laminin epitopes and collagen on an artificial hybrid matrix construct

AU - Sur, Shantanu

AU - Guler, Mustafa O.

AU - Webber, Matthew J.

AU - Pashuck, Eugene T.

AU - Ito, Masao

AU - Stupp, Samuel I

AU - Launey, Thomas

PY - 2014

Y1 - 2014

N2 - The extracellular matrix (ECM) creates a dynamic environment around the cells in the developing central nervous system, providing them with the necessary biochemical and biophysical signals. Although the functions of many ECM molecules in neuronal development have been individually studied in detail, the combinatorial effects of multiple ECM components are not well characterized. Here we demonstrate that the expression of collagen and laminin-1 (lam-1) are spatially and temporally correlated during embryonic and post-natal development of the cerebellum. These changes in ECM distribution correspond to specific stages of Purkinje neuron (PC) migration, somatic monolayer formation and polarization. To clarify the respective roles of these ECM molecules on PC development, we cultured cerebellar neurons on a hybrid matrix comprised of collagen and a synthetic peptide amphiphile nanofiber bearing a potent lam-1 derived bioactive IKVAV peptide epitope. By systematically varying the concentration and ratio of collagen and the laminin epitope in the matrix, we could demonstrate a synergistic relationship between these two ECM components in controlling multiple aspects of PC maturation. An optimal ratio of collagen and IKVAV in the matrix was found to promote maximal PC survival and dendrite growth, while dendrite penetration into the matrix was enhanced by a high IKVAV to collagen ratio. In addition, the laminin epitope was found to guide PC axon development. By combining our observations in vivo and in vitro, we propose a model of PC development where the synergistic effects of collagen and lam-1 play a key role in migration, polarization and morphological maturation of PCs. This journal is

AB - The extracellular matrix (ECM) creates a dynamic environment around the cells in the developing central nervous system, providing them with the necessary biochemical and biophysical signals. Although the functions of many ECM molecules in neuronal development have been individually studied in detail, the combinatorial effects of multiple ECM components are not well characterized. Here we demonstrate that the expression of collagen and laminin-1 (lam-1) are spatially and temporally correlated during embryonic and post-natal development of the cerebellum. These changes in ECM distribution correspond to specific stages of Purkinje neuron (PC) migration, somatic monolayer formation and polarization. To clarify the respective roles of these ECM molecules on PC development, we cultured cerebellar neurons on a hybrid matrix comprised of collagen and a synthetic peptide amphiphile nanofiber bearing a potent lam-1 derived bioactive IKVAV peptide epitope. By systematically varying the concentration and ratio of collagen and the laminin epitope in the matrix, we could demonstrate a synergistic relationship between these two ECM components in controlling multiple aspects of PC maturation. An optimal ratio of collagen and IKVAV in the matrix was found to promote maximal PC survival and dendrite growth, while dendrite penetration into the matrix was enhanced by a high IKVAV to collagen ratio. In addition, the laminin epitope was found to guide PC axon development. By combining our observations in vivo and in vitro, we propose a model of PC development where the synergistic effects of collagen and lam-1 play a key role in migration, polarization and morphological maturation of PCs. This journal is

UR - http://www.scopus.com/inward/record.url?scp=84900298407&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84900298407&partnerID=8YFLogxK

U2 - 10.1039/c3bm60228a

DO - 10.1039/c3bm60228a

M3 - Article

AN - SCOPUS:84900298407

VL - 2

SP - 903

EP - 914

JO - Biomaterials Science

JF - Biomaterials Science

SN - 2047-4830

IS - 6

ER -