A novel method to produce immobilised biomolecular concentration gradients to study cell activities: design and modelling

Mol Biotechnol. 2012 Feb;50(2):99-107. doi: 10.1007/s12033-011-9411-9.

Abstract

It is well known that many cell functions are activated by chemical signals with a time and space-dependent profile. To mimic these profiles in vitro, it is necessary to develop a system that is able to generate concentration gradients with a resolution similar to that perceived by cells, which is around nanomolar with a spatial resolution of a few tens of microns. Many devices capable of generating steady-state concentration gradients have been developed using continuous flow micro-fluidic techniques. However, these systems cannot reproduce the immobilised concentration gradients that are present in the extracellular matrix. For this reason, we have developed a new gradient generator to enable precise and reproducible studies on the effects of immobilised concentration gradients on cell behaviour. A well-known gradient of a desired molecule was generated on the bottom surface of a hydrogel, which was then used as a stamp to immobilise the molecule on a functionalised substrate. A concentration gradient was thus obtained using a simple silane-based chemical reaction. To validate the method, image analysis was performed on glass slides printed with fluorescein isothiocyanate (FITC)- collagen and FITC-poly-lysine concentration gradients. Preliminary cell adhesion tests were also carried out by seeding NIH-3T3 and mesencephalic cells on lab-glass slides printed with concentration profiles of collagen and poly-lysine, respectively.

MeSH terms

  • Animals
  • Biotechnology / instrumentation*
  • Biotechnology / methods
  • Cell Adhesion*
  • Cells, Cultured
  • Collagen / chemistry
  • Equipment Design
  • Fluorescein-5-isothiocyanate / chemistry
  • Fluorescent Dyes / chemistry
  • Glass
  • Hydrogels
  • Mesencephalon / cytology
  • Mice
  • Models, Theoretical
  • Polylysine / chemistry
  • Reproducibility of Results
  • Silanes / chemistry

Substances

  • Fluorescent Dyes
  • Hydrogels
  • Silanes
  • Polylysine
  • Collagen
  • Fluorescein-5-isothiocyanate