English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Nano-patterned, mechano-tunable, ECM mimetic substrates for cell adhesion studies under strain

Aragüés Rioja, B. (2011). Nano-patterned, mechano-tunable, ECM mimetic substrates for cell adhesion studies under strain. PhD Thesis, Ruprecht-Karls-Universität Heidelberg, Heidelberg. Retrieved from http://www.ub.uni-heidelberg.de/archiv/12357.

Item is

Files

show Files
hide Files
:
Aragues_Diss_2011.pdf (Any fulltext), 70MB
 
File Permalink:
-
Name:
Aragues_Diss_2011.pdf
Description:
-
OA-Status:
Visibility:
Restricted (Max Planck Institute for Medical Research, MHMF; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show
hide
Description:
-
OA-Status:
Description:
-
OA-Status:

Creators

show
hide
 Creators:
Aragüés Rioja, Borja1, Author           
Affiliations:
1Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society, ou_2364731              

Content

show
hide
Free keywords: mechanosensing , focal adhesions , integrin signaling , elastic PEG hydrogel , cell adhesion
 Abstract: Adherent cells are sensitive to physical and chemical cues in their environment and can adapt their response accordingly. Receptors in cells membrane are crucial elements in the recognition of such signals by binding external ligands (key-and-lock principle). Thereby these receptors and associated proteins transduce external cues in internal signals. Chemical nature of the ligands and their spatial arrangement can provide important information to the cells. In particular, spatial clustering of the ligands at the nanometer scale is considered to be a general principle by which the signal transduction of many biological processes gets modulated. Examples are the formation of focal adhesions (FAs) or of the immunological synapse. To investigate such clustering effects at the molecular scale, there is an immanent need for the precise chemical modification of surfaces. Therefore, the aim of this work was to (i) develop a substrate on which the spatial arrangement of bound particles could be precisely controlled and varied at the nanometer scale, and (ii) to demonstrate the utility of such substrates in cell adhesion studies. During this work an elastic poly(ethyleneglycol)-diacrylate (PEG-DA) hydrogel (HG) was used as carrier substrate on which an array of gold nano-particles (AuNPs) with well defined inter-particle distances (Delta L) was immobilized. Delta L could be successfully varied at the nanometer scale by mechanical stretching of the carrier substrate. For cell adhesion studies the AuNPs were functionalized with a c(RGDfK) peptide so that integrin binding was preferentially invoked. Due to the protein repellent properties of PEG, the AuNPs constituted the only anchor points on which cells could adhere. Thereby nanometer precision on the spatial arrangement of the ligands was achieved. To show the versatility of PEG-DA HGs as bio-mimetic substrates, the surfaces of a series of HGs were homogeneously functionalized with Fibronectin (FN). Strain applied to the HGs was successfully transmitted to cells and FAs and their reaction to the strain and to the change in inter-ligand distances was monitored and analyzed. The anisotropy generated in the ligand array by the uni-axial stretching influenced cell adhesion. FAs reaction was more prominent when stretched on HGs + FN than on HGs + AuNPs + RGD. In summary, fabrication of a material system for the dynamic variation of Delta L in the tens of nanometers was accomplished in this work. By rendering these substrates bio-mimetic, cell adhesion studies with dynamic variation of inter-ligand distances could be performed.

Details

show
hide
Language(s): eng - English
 Dates: 2011-05-202011-11-292011
 Publication Status: Issued
 Pages: 126
 Publishing info: Heidelberg : Ruprecht-Karls-Universität Heidelberg
 Table of Contents: -
 Rev. Type: -
 Identifiers: eDoc: 563673
URN: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:bsz:16-heidok-123570
URI: http://www.ub.uni-heidelberg.de/archiv/12357
 Degree: PhD

Event

show

Legal Case

show

Project information

show

Source

show