Membrane-Mimetic Systems

MembraneLipid-based membranes have attracted considerable attention due to their potential application as tools to probe cellular and molecular interactions and as bioactive coatings for biosensor or medical implant applications. In particular, phospholipids differing in chemical composition, degree of saturation and size have provided primary building blocks for membrane-based structures of varying geometry because of their intrinsic biocompatibility, high packing density, and propensity to form lamellar systems. Nonetheless, inherently limited stability continues to restrict the use non-covalently associated lipid membrane systems to transient or short-term applications. Prior studies by our group have led to the fabrication of supported membrane-like films by photocrosslinking of polymerizable lipids. Significantly, the ability to integrate bioactive membrane proteins has been demonstrated. We have also synthesized lipid bolaamphiphiles, which are comprised of two polar head groups separated by one or two hydrophobic spacer groups as an alternate approach for fabricating membrane-mimetic materials comprised of membrane-spanning constituents.

MembraneIn serving as mobile reservoirs for enzymatically active transmembrane proteins, we believe that properties can be incorporated into thin films that may be able to enhance the performance of a variety of artificial organs, cell transplants, and biosensor systems. For example, the arterial endothelium displays anticoagulant activity principally through the expression of membrane-bound thrombomodulin (TM) and heparan sulfate (HS). Membrane–mimetic thin films containing thrombomodulin (TM) and/or heparin have been produced and their capacity to inhibit thrombin generation evaluated in a continuous flow system. Surface bound TM and heparin nearly abolished steady-state thrombin responses produced by tissue factor. Our research group has a number of projects focused on the design of anti-thrombogenic surfaces, as well as the development and application of computational models of surface-induced thrombosis.

Marra KG, Winger TM, Hanson SR, Chaikof EL. Cytomimetic biomaterials. 1. In-situ polymerization of phospholipids on an alkylated surface. Macromolecules 1997; 30:6483-6487.

Faucher KM, Sun XL, Chaikof EL. Fabrication and characterization of glycocalyx-mimetic surfaces. Langmuir 2003; 19:1664-1670.

Sun XL, Stabler CA, Cazalis CS, Chaikof EL. Carbohydrate and protein immobilization onto solid surfaces by sequential Diels-Alder and azide-alkyne cycloadditions. Bioconjugate Chemistry 2006; 17:52-57.

Tseng PY, Rele S, Sun, X-L, Chaikof EL. Membrane–mimetic films containing thrombomodulin and heparin inhibit tissue factor-induced thrombin generation in a flow model. Biomaterials 2006; 27:2637–2650.

Faucher KM, Wannant S, Caves J, Sun X-L, Apkarian RP, Chaikof EL. Fabrication of a phospholipid membrane-mimetic film on the luminal surface of an ePTFE vascular graft. Biomaterials 2006; 27:3473-3481.

Krishnamurthy VR, Wilson JT, Cui W, Song XZ, Lasanajak Y, Cummings RD, Chaikof EL. Chemoselective immobilization of peptides on abiotic and cell surfaces at controlled densities. Langmuir 2010; 26: 7675–7678.

Jordan SW, Chaikof EL. Simulated surface-induced thrombin generation in a flow field. Biophys J 2011; 101:276-286

Qu Z, Muthukrishnan S, Urlam MK, Haller CA, Jordan SW, Kumar VA, Marzec UM, Elkasabi Y, Lahann J, Hanson SR, Chaikof EL. A biologically active surface enzyme assembly that attenuates thrombus formation. Advanced Functional Materials 2011; 21: 4736–4743.