title: Fibronectin conformational changes induced by adsorption to liposomes.
abstract: One of the major drawbacks of drug delivery techniques that utilize liposomes as carriers is that they are often cleared from the body before they can deliver their therapeutic cargo. It is well known that serum proteins can adsorb to these drug delivery vehicles and influence their uptake by phagocytic cells. For this reason, protein adsorption to liposomes has been extensively quantified, and strategies have been developed to minimize protein adsorption to improve drug delivery. However, the conformation of proteins on surfaces can play an even greater role in controlling cell behavior than the quantity of adsorbed protein. We have therefore used fluorescence resonance energy transfer (FRET) to measure changes in the structure of fibronectin (Fn)--a key serum protein involved in phagocytosis--upon interaction with phosphatidylcholine (PC) liposomes. Our experiments reveal that fibronectin opens up from its inactive, compact conformation upon interaction with gel phase PC liposomes. We also used FRET to estimate a physiologically relevant dissociation constant, KD=1.1 nM, for the interaction. Conformational changes in serum proteins may result in the exposure of otherwise concealed recognition sites and therefore influence the interaction of liposomes with phagocytic cells.
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Halter
authors.forename: Meher
authors.initials: M
authors.lastname: Antia
authors.forename: Viola
authors.initials: V
authors.lastname: Vogel
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000327:Adsorption; D016503:Drug Delivery Systems; D005353:Fibronectins / Q000737:chemistry*; D031541:Fluorescence Resonance Energy Transfer; D005782:Gels; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D010587:Phagocytosis; D011487:Protein Conformation
chemical_list: D005353:Fibronectins; D005782:Gels; D008051:Lipid Bilayers; D008081:Liposomes; D015060:1,2-Dipalmitoylphosphatidylcholine