Bioinspired vesicle restraint and mobilization using a biopolymer scaffold.
Biology employs vesicles to package molecules (e.g., neurotransmitters) for their targeted delivery in response to specific spatiotemporal stimuli. Biology is also capable of employing localized stimuli to exert an additional control on vesicle trafficking; intact vesicles can be restrained (or mobilized) by association with (or release from) a cytoskeletal scaffold. We mimic these capabilities by tethering vesicles to a biopolymer scaffold that can undergo (i) stimuli-responsive network formation (for vesicle restraint) and (ii) enzyme-catalyzed network cleavage (for vesicle mobilization). Specifically, we use the aminopolysaccharide chitosan as our scaffold and graft a small number of hydrophobic moieties onto its backbone. These grafted hydrophobes can insert into the bilayer to tether vesicles to the scaffold. Under acidic conditions, the vesicles are not restrained by the hydrophobically modified chitosan (hm-chitosan) because this scaffold is soluble. Increasing the pH to neutral or basic conditions allows chitosan to form interpolymer associations that yield a strong, insoluble restraining network. Enzymatic hydrolysis of this scaffold by chitosanase cleaves the network and mobilizes intact vesicles. Potentially, this approach will provide a controllable means to store and liberate vesicle-based reagents/therapeutics for microfluidic/medical applications.
Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, Maryland 20742, USA.
Chao
C
Zhu
Jae-Ho
JH
Lee
Srinivasa R
SR
Raghavan
Gregory F
GF
Payne
D048271:Chitosan / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008567:Membranes, Artificial
D008567:Membranes, Artificial; D048271:Chitosan