English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Nanoscale integrin ligand patterns determine melanoma cell behavior

MPS-Authors
/persons/resource/persons75725

Kruss,  Sebastian
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;
Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany;

External Resource
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Amschler, K., Erpenbeck, L., Kruss, S., & Schön, M. P. (2014). Nanoscale integrin ligand patterns determine melanoma cell behavior. ACS Nano, 8(9), 9113-9125. doi:10.1021/nn502690b.


Cite as: https://hdl.handle.net/11858/00-001M-0000-0024-5F7B-7
Abstract
Cells use integrin receptors to adhere onto surfaces by binding to ligands such as the arginine-glycine-aspartic acid (RGD) motif. Cancer cells make use of this adhesion process, which has motivated the development of integrin-directed drugs. However, those drugs may exert paradoxical effects on tumor progression, which raises the question of how integrin function is governed in tumor cells on the nanoscale. We have utilized precisely defined and tunable RGD ligand site densities spanning 1 order of magnitude, i.e., 103 to 1145 ligand sites/μm2, by using RGD-functionalized gold nanoparticle patterns immobilized on glass by block copolymer (micellar) nanolithography. In an αVβ3 integrin-dependent fashion, human melanoma cells spread, formed focal contacts, and reorganized cytoskeletal fibers on a physiologically relevant RGD density of 349 sites/μm2. Intriguingly, low doses of solute RGD “shifted” the optimal densities of immobilized ligand along with corresponding melanoma cell integrin clusters and cytoskeletal changes toward those typical for “intermediate” ligand presentation. Consequently, melanoma cells were forced into a “permissive” state, optimizing interactions with suboptimal nanostructured biomimetic surfaces, thus providing an explanation for the seemingly paradoxical effects on tumor progression and a potential clue for individualized antitumoral therapies.