title: N-terminal specific conjugation of extracellular matrix proteins to 2-pyridinecarboxaldehyde functionalized polyacrylamide hydrogels.
abstract: Polyacrylamide hydrogels have been used extensively to study cell responses to the mechanical and biochemical properties of extracellular matrix substrates. A key step in fabricating these substrates is the conjugation of cell adhesion proteins to the polyacrylamide surfaces, which typically involves nonspecifically anchoring these proteins via side-chain functional groups. This can result in a loss of presentation control and altered bioactivity. Here, we describe a new functionalization strategy in which we anchor full-length extracellular matrix proteins to polyacrylamide substrates using 2-pyridinecarboxaldehyde, which can be co-polymerized into polyacrylamide gels and used to immobilize proteins by their N-termini. This one-step reaction proceeds under mild aqueous conditions and does not require additional reagents. We demonstrate that these substrates can readily conjugate to various extracellular matrix proteins, as well as promote cell adhesion and spreading. Notably, this chemistry supports the assembly and cellular remodeling of large collagen fibers, which is not observed using conventional side-chain amine-conjugation chemistry.
authors.affiliation: Department of Chemistry, University of California, Berkeley, CA 94720, USA; Department of Bioengineering, University of California, Berkeley, CA 94720, USA.
authors.forename: Jessica P
authors.initials: JP
authors.lastname: Lee
authors.affiliation: Department of Bioengineering, University of California, Berkeley, CA 94720, USA; UC Berkeley-UCSF Graduate Program in Bioengineering, Berkeley, CA 94720, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Kassianidou
authors.affiliation: Department of Chemistry, University of California, Berkeley, CA 94720, USA.
authors.forename: James I
authors.initials: JI
authors.lastname: MacDonald
authors.affiliation: Department of Chemistry, University of California, Berkeley, CA 94720, USA; Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Francis
authors.affiliation: Department of Bioengineering, University of California, Berkeley, CA 94720, USA; UC Berkeley-UCSF Graduate Program in Bioengineering, Berkeley, CA 94720, USA; Department of Chemical and Biomolecular Engineering, University of California, Berkeley CA 94720, USA. Electronic address: skumar@berkeley.edu.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kumar
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002417:Cattle; D002448:Cell Adhesion; D002460:Cell Line; D003094:Collagen / Q000737:chemistry; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D006244:Hardness; D006801:Humans; D055595:Mechanical Phenomena; D051379:Mice; D011725:Pyridines / Q000737:chemistry*
chemical_list: D000180:Acrylic Resins; D001672:Biocompatible Materials; D016326:Extracellular Matrix Proteins; D011725:Pyridines; C016680:polyacrylamide gels; C051439:pyridinecarboxaldehyde; D003094:Collagen