AVS 46th International Symposium
    Applied Surface Science Division Tuesday Sessions
       Session AS-TuP

Paper AS-TuP14
Control of Intracellular Signal Transduction Using Self-Assembled Monolayers of Alkylthiolates on Gold

Tuesday, October 26, 1999, 5:30 pm, Room 4C

Session: Poster Session
Presenter: K.B. McClary, Colorado State University
Authors: K.B. McClary, Colorado State University
D.G. Grainger, Colorado State University
Correspondent: Click to Email
Self-assembled monolayers of terminally-functionalized alkylthiolates on gold have been used to interrogate cell-biomaterial surface interactions at the extracellular and intracellular level. The goal of this research is to provide molecular level information on the surface determinants necessary to produce predictable, controllable biological responses to implanted materials. Various aspects of "outside-in" communication between cells and material surfaces have been investigated. Formation of focal contacts and stress fibers, early indicators of effective intracellular signaling, was observed to be surface-chemistry dependent, and correlated with protein behavior on different surface chemistries. The primary cellular regulators of these events were examined using well-controlled alkylthiol surface chemistries. Activation states of the GTPase RhoA were determined and shown to be surface chemistry-dependent. RhoGDI levels and intracellular localization were also shown to be surface-chemistry dependent. Cells cultured on -CH3 terminated SAMs, which normally exhibit a low growth phenotype, were transfected with a constitutively active RhoA mutant. Transfected cells exhibited significant increases in cell length. However, no focal contact formation was observed. These results show that genetic alteration of intracellular regulators is incapable of overcoming the lack of extracellular stimuli, in the form of adsorbed ECM proteins, present on -CH3 terminated SAM surfaces. In summary, extracellular and intracellular information indicates that surface chemistry is capable of modulating communication between a cell and its extracellular environment. These data provide new, valuable molecular level information necessary to develop rational cause and effect relationships between a material's surface chemistry and biological response.