Nanoscale Assembly in Biological Systems: From Neuronal Cytoskeletal Proteins to Curvature Stabilizing Lipids

Abstract

The review will describe experiments inspired by the rich variety of bundles and networks of interacting microtubules (MT), neurofilaments, and filamentous-actin in neurons where the nature of the interactions, structures, and structure-function correlations remain poorly understood. We describe how three-dimensional (3D) MT bundles and 2D MT bundles may assemble, in cell free systems in the presence of counter-ions, revealing structures not predicted by polyelectrolyte theories. Interestingly, experiments reveal that the neuronal protein tau, an abundant MT-associated-protein in axons, modulates the MT diameter providing insight for the control of geometric parameters in bio-nanotechnology. In another set of experiments we describe lipid-protein-nanotubes, and lipid nano-tubes and rods, resulting from membrane shape evolution processes involving protein templates and curvature stabilizing lipids. Similar membrane shape changes, occurring in cells for the purpose of specific functions, are induced by interactions between membranes and proteins. The biological materials systems described have applications in bio-nanotechnology.

Modulating self-assembly of a nanotape-forming peptideamphiphile with an oppositely charged surfactant

“…Divalent cations are known to have remarkable properties in polyelectrolyte solutions and other self-assembling systems. [38][39][40][41][42] In addition, Manning condensation 43,44 is well documented for polyelectrolyte solutions such as DNA or poly(styrene sulfonate). 38,39,41 The presence of condensed counterions in the present system, can in fact be justified by applying the Manning condensation threshold criterion to the self-assembled C 16 -KTTKS structure.…”

Polyelectrolyte properties of filamentous biopolymers and their consequences in biological fluids

“…However, theoretical studies suggest that numerous other morphologies of semiflexible or rigid polymers mediated by multivalent counterions can form at counterion concentrations lower than those required for collapse into bundles, if the biopolymers are sufficiently long and the samples can be prepared with minimal shearing 25, 26 . Scattering and imaging techniques have revealed fascinating structures, often lamellar or tubular, arising from the interaction of DNA 69, 70 , F-actin 13, 71 , microtubules 15 , and neurofilaments 72 with multivalent counterions, especially cationic lipids. X-ray scattering studies have been especially effective in discriminating nm scale structures within polyelectrolyte systems that have been aggregated by multivalent counterions.…”

“…For example, X-ray scattering has revealed dynamic clusters of counterions near patches of F-actin that are enriched in negative charge 73 , and studies of neurofilaments have revealed fascinating liquid crystalline structures formed by the polypeptides that extend from the filament surface and make contact with each other 59, 74 . Some of these structures were not predicted by theory, and a range of structures formed by polyelectrolyte systems have been summarized in recent reviews 8, 72 .…”

Identification of Lipid Heterogeneity and Diversity in the Developing Human Brain

“…While there is significant functional relevance within neuronal axons, the lipids measured here within the soma represent biological relevance associated with cell shape, protein anchoring, and developmental processes prior to extensive morphological maturation. 31 , 32 …”