Cell surface engineering with polyelectrolyte multilayer thin films

J Am Chem Soc. 2011 May 11;133(18):7054-64. doi: 10.1021/ja110926s. Epub 2011 Apr 14.

Abstract

Layer-by-layer assembly of polyelectrolyte multilayer (PEM) films represents a bottom-up approach for re-engineering the molecular landscape of cell surfaces with spatially continuous and molecularly uniform ultrathin films. However, fabricating PEMs on viable cells has proven challenging owing to the high cytotoxicity of polycations. Here, we report the rational engineering of a new class of PEMs with modular biological functionality and tunable physicochemical properties which have been engineered to abrogate cytotoxicity. Specifically, we have discovered a subset of cationic copolymers that undergoes a conformational change, which mitigates membrane disruption and facilitates the deposition of PEMs on cell surfaces that are tailorable in composition, reactivity, thickness, and mechanical properties. Furthermore, we demonstrate the first successful in vivo application of PEM-engineered cells, which maintained viability and function upon transplantation and were used as carriers for in vivo delivery of PEMs containing biomolecular payloads. This new class of polymeric film and the design strategies developed herein establish an enabling technology for cell transplantation and other therapies based on engineered cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / chemical synthesis
  • Biocompatible Materials / chemistry*
  • Biocompatible Materials / toxicity
  • Bioengineering*
  • Cell Membrane / chemistry*
  • Electrolytes / chemical synthesis
  • Electrolytes / chemistry
  • Electrolytes / toxicity
  • Islets of Langerhans / chemistry
  • Islets of Langerhans Transplantation*
  • Mice
  • Polyamines / chemical synthesis
  • Polyamines / chemistry
  • Polyamines / toxicity
  • Polyelectrolytes
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / toxicity
  • Polylysine / analogs & derivatives
  • Polylysine / chemical synthesis
  • Polylysine / chemistry
  • Polylysine / toxicity
  • Polymers / chemical synthesis
  • Polymers / chemistry*
  • Polymers / toxicity

Substances

  • Biocompatible Materials
  • Electrolytes
  • Polyamines
  • Polyelectrolytes
  • Polymers
  • polycations
  • polylysine-graft-(poly(ethylene glycol))
  • Polylysine
  • Polyethylene Glycols