Effect of RGD secondary structure and the synergy site PHSRN on cell adhesion, spreading and specific integrin engagement

Sarah E. Ochsenhirt; Efrosini Kokkoli; James B. McCarthy; Matthew Tirrell

doi:10.1016/j.biomaterials.2005.12.012

Effect of RGD secondary structure and the synergy site PHSRN on cell adhesion, spreading and specific integrin engagement

Sarah E. Ochsenhirt, Efrosini Kokkoli, James B. McCarthy, Matthew Tirrell

Research output: Contribution to journal › Article › peer-review

113 Scopus citations

Abstract

The relationship between the form of cell adhesion, ligand presentation, and cell receptor function was characterized using model Langmuir-Blodgett supported films, containing lipid-conjugated peptide ligands, in which isolated variables of the ligand presentation were systematically altered. First, the conformation of an adhesive Arginine-Glycine-Aspartic acid (RGD) peptide was varied by synthesizing linear and looped RGD peptide-containing amphiphiles and subsequently measuring the impact on the function of human umbilical vein endothelial cells. Secondly, the contribution of non-contiguous ligands to cellular engagement was assessed using multi-component biomimetic films. The peptide amphiphiles were composed of fibronectin-derived headgroups-GRGDSP, and its synergy site Pro-His-Ser-Arg-Asn (PHSRN)-attached to hydrocarbon tails. The peptide amphiphiles were diluted using polyethylene glycol (PEG) amphiphiles, where PEG inhibited non-specific cell adhesion. Cells adhered and spread on GRGDSP/PEG systems in a dose-dependent manner. The presentation of GRGDSP influenced integrin cell surface receptor specificity. Results demonstrated that β₁-containing integrins mediated adhesion to the linear GRGDSP presentation to a greater extent than did the α_vβ₃ integrin, and looped GRGDSP preferentially engaged α_vβ₃. GRGDSP/PHSRN/PEG mixtures that closely mimicked the RGD-PHSRN distance in fibronectin, enhanced cell spreading over their two-component analogues. This study demonstrated that controlling the microenvironment of the cell was essential for biomimetics to modulate specific binding and subsequent signaling events.

Original language	English (US)
Pages (from-to)	3863-3874
Number of pages	12
Journal	Biomaterials
Volume	27
Issue number	20
DOIs	https://doi.org/10.1016/j.biomaterials.2005.12.012
State	Published - Jul 2006

Bibliographical note

Funding Information:
This work was partially supported by the MRSEC Program of the National Science Foundation under Award no. DMR00-80034 at the University of California, Santa Barbara and partially by the University of Minnesota MRSEC Artificial Tissues Program (DMR99-09364).

Keywords

Cyclic RGD
HUVEC
Looped RGD
PHSRN
α5β1 integrin
αβ integrin

Publisher link

10.1016/j.biomaterials.2005.12.012

Find It

Find It at U of M Libraries

Cite this

@article{59c91b0b6ce74396bde6e773cf045369,

title = "Effect of RGD secondary structure and the synergy site PHSRN on cell adhesion, spreading and specific integrin engagement",

abstract = "The relationship between the form of cell adhesion, ligand presentation, and cell receptor function was characterized using model Langmuir-Blodgett supported films, containing lipid-conjugated peptide ligands, in which isolated variables of the ligand presentation were systematically altered. First, the conformation of an adhesive Arginine-Glycine-Aspartic acid (RGD) peptide was varied by synthesizing linear and looped RGD peptide-containing amphiphiles and subsequently measuring the impact on the function of human umbilical vein endothelial cells. Secondly, the contribution of non-contiguous ligands to cellular engagement was assessed using multi-component biomimetic films. The peptide amphiphiles were composed of fibronectin-derived headgroups-GRGDSP, and its synergy site Pro-His-Ser-Arg-Asn (PHSRN)-attached to hydrocarbon tails. The peptide amphiphiles were diluted using polyethylene glycol (PEG) amphiphiles, where PEG inhibited non-specific cell adhesion. Cells adhered and spread on GRGDSP/PEG systems in a dose-dependent manner. The presentation of GRGDSP influenced integrin cell surface receptor specificity. Results demonstrated that β1-containing integrins mediated adhesion to the linear GRGDSP presentation to a greater extent than did the αvβ3 integrin, and looped GRGDSP preferentially engaged αvβ3. GRGDSP/PHSRN/PEG mixtures that closely mimicked the RGD-PHSRN distance in fibronectin, enhanced cell spreading over their two-component analogues. This study demonstrated that controlling the microenvironment of the cell was essential for biomimetics to modulate specific binding and subsequent signaling events.",

keywords = "Cyclic RGD, HUVEC, Looped RGD, PHSRN, α5β1 integrin, αβ integrin",

author = "Ochsenhirt, {Sarah E.} and Efrosini Kokkoli and McCarthy, {James B.} and Matthew Tirrell",

note = "Funding Information: This work was partially supported by the MRSEC Program of the National Science Foundation under Award no. DMR00-80034 at the University of California, Santa Barbara and partially by the University of Minnesota MRSEC Artificial Tissues Program (DMR99-09364).",

year = "2006",

month = jul,

doi = "10.1016/j.biomaterials.2005.12.012",

language = "English (US)",

volume = "27",

pages = "3863--3874",

journal = "Biomaterials",

issn = "0142-9612",

publisher = "Elsevier Ltd",

number = "20",

}

TY - JOUR

T1 - Effect of RGD secondary structure and the synergy site PHSRN on cell adhesion, spreading and specific integrin engagement

AU - Ochsenhirt, Sarah E.

AU - Kokkoli, Efrosini

AU - McCarthy, James B.

AU - Tirrell, Matthew

N1 - Funding Information: This work was partially supported by the MRSEC Program of the National Science Foundation under Award no. DMR00-80034 at the University of California, Santa Barbara and partially by the University of Minnesota MRSEC Artificial Tissues Program (DMR99-09364).

PY - 2006/7

Y1 - 2006/7

N2 - The relationship between the form of cell adhesion, ligand presentation, and cell receptor function was characterized using model Langmuir-Blodgett supported films, containing lipid-conjugated peptide ligands, in which isolated variables of the ligand presentation were systematically altered. First, the conformation of an adhesive Arginine-Glycine-Aspartic acid (RGD) peptide was varied by synthesizing linear and looped RGD peptide-containing amphiphiles and subsequently measuring the impact on the function of human umbilical vein endothelial cells. Secondly, the contribution of non-contiguous ligands to cellular engagement was assessed using multi-component biomimetic films. The peptide amphiphiles were composed of fibronectin-derived headgroups-GRGDSP, and its synergy site Pro-His-Ser-Arg-Asn (PHSRN)-attached to hydrocarbon tails. The peptide amphiphiles were diluted using polyethylene glycol (PEG) amphiphiles, where PEG inhibited non-specific cell adhesion. Cells adhered and spread on GRGDSP/PEG systems in a dose-dependent manner. The presentation of GRGDSP influenced integrin cell surface receptor specificity. Results demonstrated that β1-containing integrins mediated adhesion to the linear GRGDSP presentation to a greater extent than did the αvβ3 integrin, and looped GRGDSP preferentially engaged αvβ3. GRGDSP/PHSRN/PEG mixtures that closely mimicked the RGD-PHSRN distance in fibronectin, enhanced cell spreading over their two-component analogues. This study demonstrated that controlling the microenvironment of the cell was essential for biomimetics to modulate specific binding and subsequent signaling events.

AB - The relationship between the form of cell adhesion, ligand presentation, and cell receptor function was characterized using model Langmuir-Blodgett supported films, containing lipid-conjugated peptide ligands, in which isolated variables of the ligand presentation were systematically altered. First, the conformation of an adhesive Arginine-Glycine-Aspartic acid (RGD) peptide was varied by synthesizing linear and looped RGD peptide-containing amphiphiles and subsequently measuring the impact on the function of human umbilical vein endothelial cells. Secondly, the contribution of non-contiguous ligands to cellular engagement was assessed using multi-component biomimetic films. The peptide amphiphiles were composed of fibronectin-derived headgroups-GRGDSP, and its synergy site Pro-His-Ser-Arg-Asn (PHSRN)-attached to hydrocarbon tails. The peptide amphiphiles were diluted using polyethylene glycol (PEG) amphiphiles, where PEG inhibited non-specific cell adhesion. Cells adhered and spread on GRGDSP/PEG systems in a dose-dependent manner. The presentation of GRGDSP influenced integrin cell surface receptor specificity. Results demonstrated that β1-containing integrins mediated adhesion to the linear GRGDSP presentation to a greater extent than did the αvβ3 integrin, and looped GRGDSP preferentially engaged αvβ3. GRGDSP/PHSRN/PEG mixtures that closely mimicked the RGD-PHSRN distance in fibronectin, enhanced cell spreading over their two-component analogues. This study demonstrated that controlling the microenvironment of the cell was essential for biomimetics to modulate specific binding and subsequent signaling events.

KW - Cyclic RGD

KW - HUVEC

KW - Looped RGD

KW - PHSRN

KW - α5β1 integrin

KW - αβ integrin

UR - http://www.scopus.com/inward/record.url?scp=33645972915&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645972915&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2005.12.012

DO - 10.1016/j.biomaterials.2005.12.012

M3 - Article

C2 - 16563498

AN - SCOPUS:33645972915

SN - 0142-9612

VL - 27

SP - 3863

EP - 3874

JO - Biomaterials

JF - Biomaterials

IS - 20

ER -

Effect of RGD secondary structure and the synergy site PHSRN on cell adhesion, spreading and specific integrin engagement

Abstract

Bibliographical note

Keywords

Publisher link

Find It

Other files and links

Fingerprint

Cite this