The Construction Of Electrochemical Controlled Bio-interfaces

Engineering the cellular environment with synthetic materials has been a long-standing challenge for biomedical research. The natural cellular environment is highly complex and dynamic, making its understanding and emulation a considerable challenge. It has been recognized that merely presenting properties (chemistry, topography, stiffness) similar to those present in the natural extracellular matrix (ECM) by a material surface is not sufficient to address current challenges in biomaterial and healthcare research. To better understand cell-material interactions and develop biomaterials for advanced applications in regenerative medicine, dynamic elements will have to be incorporated within the biointerface.This thesis focus on developing electrochemically controlled biological smart surfaces based on self-assembled monolayers. The smart surfaces were characterized by electrochemistry, electrochemical surface-enhanced Raman spectroscopy (EC-SERS), AC impedance, X-ray photoelectron spectroscopy (XPS) to monitor the electrochemical controlled surface reaction. Then we investigated cell adhesion and migration on this smart surface. Specific contents include:1. We successfully established the electrochemical surface enhanced Raman spectroscopy (EC-SERS) in our own laboratory. It laid foundation for the in situ monitoring of the electrochemically controlled surface reaction.2. We investigated an electrochemically switched heterocyclization reaction on hydroquinone-terminated self-assembled monolayers (SAMs). This reaction involves an electrochemically modulated hydroquinone/benzoquinone transformation step in the SAMs and a subsequent heterocyclization step taking place between the electrochemically generated benzoquinone moieties in SAMs and Lcysteine in solution. The reaction process was monitored by XPS and electrochemical surface-enhanced Raman spectroscopy (EC-SERS). The surface reaction proceeds as a two-step reaction to give a benzothiazine product, which is in contrast to the much more complicated multiple step reactions in solution. This result suggests that the tight molecular packing in the SAMs does not hinder the intramolecular heterocylization reaction, but prevents the intermolecular coupling reaction from happening. This work provides insights to the control and detection of biomolecule related multistep reactions occurring at solid-liquid interface.3. We established an electrochemically switched smart surface for controlled peptide immobilization and conformation control. This dynamic surface is based on self-assembled monolayers (SAMs) containing surface-bound trimethoxybenzene moieties, which can undergo electrochemically modulated surface activation to be stepwisely converted to two catechol derivatives. This new smart surface can be used to realize stepwise immobilization of a peptide, and more importantly, to control peptide conformation on a surface. We demonstrate herein that with one electrochemical activation step, a linear peptide containing an RGD sequence can be attached onto the SAMs. With the subsequence activation step, the attached linear RGD peptide can be converted into cyclic conformation. The SAMs bounded with linear and cyclic RGD exhibit different adhesion behaviors to fibroblasts cells. The reaction procedure can be well-monitored by cyclic voltammetry (CV), electrochemical surface enhanced Raman microscopy (EC-SERS), and X-ray photoelectron spectroscopy (XPS). It is believed this robust smart surface can find wide applications in surface immobilization of bioactive moieties.4. We developed an electrically switchable smart surface for controlling cell adhesion and migration. This dynamic surface is based-on self-assembled monolayers (SAMs) containing RGD peptide with positively charged quaternary ammonium end group. Application of a positive potential repels the end-group to result in linear RGD, whereas a negative potential can attract the end-group to the surface to form a cyclic RGD. The cyclic RGD allows a markedly higher number of cell adhesion than the linear RGD. By combining a microfluidic chip, we realized control of cell adhesion in specific areas and selective release of the cells which shows slower migration speed on cyclic RGD modified surface than on surface modified by linear RGD. We believe that this robust smart surface can find wide applications in surface immobilization of bio-active moieties and related research ranging from cell biology to tissue engineering.