Peptide-Folding Triggered Phase Separation and Lipid Membrane Destabilization in Cholesterol-Rich Lipid Vesicles

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Utterström, JohannaLinköpings universitet,Biofysik och bioteknik,Tekniska fakulteten (author)

Peptide-Folding Triggered Phase Separation and Lipid Membrane Destabilization in Cholesterol-Rich Lipid Vesicles

Article/chapterEnglish2022

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2022-04-01
AMER CHEMICAL SOC,2022
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LIBRIS-ID:oai:DiVA.org:liu-201426
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-201426URI
https://doi.org/10.1021/acs.bioconjchem.2c00115DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:149500481URI

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Language:English
Summary in:English

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Funding Agencies|Swedish Research Council (VR) [2017-04475]; Swedish Cancer Foundation [CAN 2017/430, 21 1603 Pj 01]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009-00971]; Swedish Foundation for Strategic Research (SFF) [FFL15-0026]; Knut and Alice Wallenberg Foundation [KAW 2016.0231]; Royal Academy of Engineering Chair in Emerging Technologies award [CiET2021\94]; Rosetrees Trust; Swedish Foundation of Strategic Research [IRC15-0065]; Swedish Foundation for Strategic Research (SSF) [IRC15-0065] Funding Source: Swedish Foundation for Strategic Research (SSF); Swedish Research Council [2017-04475] Funding Source: Swedish Research Council
Liposome-based drug delivery systems are widely used to improve drug pharmacokinetics but can suffer from slow and unspecific release of encapsulated drugs. Membrane-active peptides, based on sequences derived or inspired from antimicrobial peptides (AMPs), could offer means to trigger and control the release. Cholesterol is used in most liposomal drug delivery systems (DDS) to improve the stability of the formulation, but the activity of AMPs on cholesterol-rich membranes tends to be very low, complicating peptide-triggered release strategies. Here, we show a de novo designed AMP-mimetic peptide that efficiently triggers content release from cholesterol-containing lipid vesicles when covalently conjugated to headgroup-functionalized lipids. Binding to vesicles induces peptide folding and triggers a lipid phase separation, which in the presence of cholesterol results in high local peptide concentrations at the lipid bilayer surface and rapid content release. We anticipate that these results will facilitate the development of peptide-based strategies for controlling and triggering drug release from liposomal drug delivery systems.

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Barriga, Hanna M. G.Karolinska Institutet,Karolinska Inst, Sweden (author)
Holme, Margaret N.Karolinska Institutet,Karolinska Inst, Sweden (author)
Selegård, RobertLinköpings universitet,Biofysik och bioteknik,Tekniska fakulteten(Swepub:liu)robse34 (author)
Stevens, Molly M.Karolinska Institutet,Karolinska Inst, Sweden; Imperial Coll London, England; Imperial Coll London, England (author)
Aili, DanielLinköpings universitet,Biofysik och bioteknik,Tekniska fakulteten(Swepub:liu)danai11 (author)
Linköpings universitetBiofysik och bioteknik (creator_code:org_t)

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In:Bioconjugate chemistry: AMER CHEMICAL SOC33:4, s. 736-7461043-18021520-4812

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