Interplay Between PEO Tether Length and Ligand Spacing Governs Cell Spreading on RGD-Modified PMMA-g-PEO Comb Copolymers
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- 作者：William Kuhlman ; Ikuo Taniguchi ; Linda G. Griffith ; Anne M. Mayes
- 刊名：Biomacromolecules
- 出版年：2007
- 出版时间：October 2007
- 年：2007
- 卷：8
- 期：10
- 页码：3206 - 3213
- 全文大小：260K
- 年卷期：v.8,no.10(October 2007)
- ISSN：1526-4602
文摘
The effects of tether length on cell adhesion to poly(methyl methacrylate)-graft-poly(ethylene oxide), PMMA-g-PEO, comb copolymer films functionalized with the adhesion peptide RGD were investigated. Copolymershaving PEO tether lengths of 10 and 22 EO segments were synthesized and coupled with a synthetic peptide thatcontained both RGD and the synergy sequence PHSRN. Cell spreading assays revealed that the longer polymertethers increased the rate of spreading and reduced the time required for fibroblasts to form focal adhesions.Fluorescence resonance energy transfer (FRET) measurements indicated a mean separation between integrin-bound peptides of 15.6 ± 1.4 nm for combs with long (22-mer) tethers, compared with 17.5 ± 1.3 nm for short(10-mer) tethers, on films of comparable peptide density (~2500 peptides/m2). The results suggest that theadded mobility afforded by the more extensible tethers encouraged the formation of focal adhesions by allowingcells to reorganize tethered peptides on the nanometer length scale. In addition, adhesion peptides were selectivelycoupled to 10-mer or 22-mer PEO tethers within a bimodal brush to investigate stratification effects on celladhesion. Peptides bound by short tethers in a bed of long unsubstituted chains resulted in surfaces that resisted,rather than promoted, cell adhesion. By contrast, when long peptide tethers were employed with short unsubstitutedchains, cell attachment and spreading were comparable to that found on a monomodal brush of long chains atequivalent peptide density.