TY - JOUR
T1 - Minor chemistry changes alter surface hydration to control fibronectin adsorption and assembly into nanofibrils
AU - Bieniek, Mateusz Krzysztof
AU - Llopis-Hernandez, Virginia
AU - Douglas, Katie
AU - Salmeron-Sanchez, Manuel
AU - Lorenz, Christian
PY - 2019/12
Y1 - 2019/12
N2 - Fibronectin (FN) is a large glycoprotein which links and transmits signals between the cell’s cytoskeleton and the extracellular matrix. FN organisation into fibrils and then fibrillogenesis can be induced with the right substrate, such as poly(ethyl acrylate) (PEA), on which FN becomes extended. Interestingly, the almost identical polymer poly(methyl acrylate) (PMA), which has one less methylene bridge (-CH2-), doesn’t cause fibrillogenesis. To investigate the difference in FN behaviour on PEA and PMA, we model the two substrates using EA and MA functionalised self-assembled monolayers (SAMs). We confirm experimentally that the EA and MA SAMs exhibit a similar behaviour in vitro to the polymers in terms of fibronectin fibrillogenesis, domain exposure and cell adhesion. Our all-atom molecular dynamics simulations of the FNIII 9-10 domains interacting with each SAM show the adsorption of these two domains on EA SAMs and no adsorption on MA SAMs. Consistently, the experiments show that FN fibrillogenesis takes place on EA SAMs but not on MA SAMs. We found that the extra methylene group in the EA headgroup leads to more motion within the headgroup that results in a markedly less dense hydration layer, which allows FN to adsorb to the substrate and therefore facilitates FN fibrillogenesis
AB - Fibronectin (FN) is a large glycoprotein which links and transmits signals between the cell’s cytoskeleton and the extracellular matrix. FN organisation into fibrils and then fibrillogenesis can be induced with the right substrate, such as poly(ethyl acrylate) (PEA), on which FN becomes extended. Interestingly, the almost identical polymer poly(methyl acrylate) (PMA), which has one less methylene bridge (-CH2-), doesn’t cause fibrillogenesis. To investigate the difference in FN behaviour on PEA and PMA, we model the two substrates using EA and MA functionalised self-assembled monolayers (SAMs). We confirm experimentally that the EA and MA SAMs exhibit a similar behaviour in vitro to the polymers in terms of fibronectin fibrillogenesis, domain exposure and cell adhesion. Our all-atom molecular dynamics simulations of the FNIII 9-10 domains interacting with each SAM show the adsorption of these two domains on EA SAMs and no adsorption on MA SAMs. Consistently, the experiments show that FN fibrillogenesis takes place on EA SAMs but not on MA SAMs. We found that the extra methylene group in the EA headgroup leads to more motion within the headgroup that results in a markedly less dense hydration layer, which allows FN to adsorb to the substrate and therefore facilitates FN fibrillogenesis
U2 - 10.1002/adts.201900169
DO - 10.1002/adts.201900169
M3 - Article
VL - 2
SP - 1
EP - 13
JO - Wiley
JF - Wiley
IS - 12
M1 - 1900169
ER -