Formation of pH-Resistant Monodispersed Polymer-Lipid Nanodiscs

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Abstract

<p class="first" id="P1">Polymer lipid nanodiscs have provided an invaluable system for structural and functional studies of membrane proteins in their near-native environment. In spite of the recent advances in the development and usage of polymer lipid nanodisc systems, lack of control over size and poor tolerance to pH and divalent metal ions are major limitations for further applications. Here we report a facile modification of a low molecular weight styrene maleic acid copolymer to form monodispersed lipid bilayer nanodiscs that show ultra-stability towards a pH range of 2.5 to 10 and divalent metal ion concentration. The macro-nanodiscs (>20 nm diameter) show magnetic-alignment properties that can be exploited for high-resolution structural studies of membrane proteins and amyloid proteins using solid-state NMR techniques. As demonstrated in this study, the new polymer, SMA-QA, nanodisc is a robust membrane mimetic tool that offers significant advantages over currently reported nanodisc systems. </p><p id="P2">Lack of control over size and poor tolerance to pH and divalent metal ions are major limitations of polymer nanodiscs. Here, a modified SMA based polymer is demonstrated to form monodispersed nanodiscs showing ultra-stability towards a pH range of 2.5 to 10 and divalent metal ions. </p><p id="P3"> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/43837113-e9e7-4930-a9de-604f9877d70c/PubMedCentral/image/nihms939177u1.jpg"/> </div> </p>

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Molecular self-assembly and nanochemistry: a chemical strategy for the synthesis of nanostructures

C. Seto, G. Whitesides, J. Mathias (1991)

Molecular self-assembly is the spontaneous association of molecules under equilibrium conditions into stable, structurally well-defined aggregates joined by noncovalent bonds. Molecular self-assembly is ubiquitous in biological systems and underlies the formation of a wide variety of complex biological structures. Understanding self-assembly and the associated noncovalent interactions that connect complementary interacting molecular surfaces in biological aggregates is a central concern in structural biochemistry. Self-assembly is also emerging as a new strategy in chemical synthesis, with the potential of generating nonbiological structures with dimensions of 1 to 10(2) nanometers (with molecular weights of 10(4) to 10(10) daltons). Structures in the upper part of this range of sizes are presently inaccessible through chemical synthesis, and the ability to prepare them would open a route to structures comparable in size (and perhaps complementary in function) to those that can be prepared by microlithography and other techniques of microfabrication.

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Molecular biomimetics: nanotechnology through biology.

Mehmet Sarikaya, Candan Tamerler, Alex Jen … (2003)

Proteins, through their unique and specific interactions with other macromolecules and inorganics, control structures and functions of all biological hard and soft tissues in organisms. Molecular biomimetics is an emerging field in which hybrid technologies are developed by using the tools of molecular biology and nanotechnology. Taking lessons from biology, polypeptides can now be genetically engineered to specifically bind to selected inorganic compounds for applications in nano- and biotechnology. This review discusses combinatorial biological protocols, that is, bacterial cell surface and phage-display technologies, in the selection of short sequences that have affinity to (noble) metals, semiconducting oxides and other technological compounds. These genetically engineered proteins for inorganics (GEPIs) can be used in the assembly of functional nanostructures. Based on the three fundamental principles of molecular recognition, self-assembly and DNA manipulation, we highlight successful uses of GEPI in nanotechnology.