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Regulation of the innate immune system by fragmented heparin-conjugated lipids on lipid bilayered membranes in vitro

Adler, Anna (author)
Uppsala University, Sweden
Fritsch, Marlene (author)
Uppsala University, Sweden
Fromell, Karin (author)
Uppsala University, Sweden
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Leneweit, Gero (author)
ABNOBA GmbH, Germany;Assoc Promot Canc Therapy, Germany
Nilsson Ekdahl, Kristina (author)
Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Uppsala University, Sweden,Linnaeus Ctr Biomat Chem, BMC
Nilsson, Bo (author)
Uppsala University, Sweden
Teramura, Yuji (author)
Uppsala University, Sweden;Cellular & Mol Biotechnol Res Inst CMB, Japan;Univ Tsukuba, Japan
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 (creator_code:org_t)
Royal Society of Chemistry, 2023
2023
English.
In: Journal of materials chemistry. B. - : Royal Society of Chemistry. - 2050-750X .- 2050-7518. ; 11:46, s. 11121-11134
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Surface modification with heparin is a powerful biomaterial coating strategy that protects against innate immunity activation since heparin is a part of the proteoglycan heparan sulfate on cell surfaces in the body. We studied the heparinization of cellular and material surfaces via lipid conjugation to a heparin-binding peptide. In the present study, we synthesized fragmented heparin (fHep)-conjugated phospholipids and studied their regulation of the innate immune system on a lipid bilayered surface using liposomes. Liposomes have versatile applications, such as drug-delivery systems, due to their ability to carry a wide range of molecules. Owing to their morphological similarity to cell membranes, they can also be used to mimic a simple cell-membrane to study protein-lipid interactions. We investigated the interaction of complement-regulators, factor H and C4b-binding protein (C4BP), as well as the coagulation inhibitor antithrombin (AT), with fHep-lipids on the liposomal surface. Herein, we studied the ability of fHep-lipids to recruit factor H, C4BP, and AT using a quartz crystal microbalance with dissipation monitoring. With dynamic light scattering, we demonstrated that liposomes could be modified with fHep-lipids and were stable up to 60 days at 4 degree celsius. Using a capillary western blot-based method (Wes), we showed that fHep-liposomes could recruit factor H in a model system using purified proteins and assist in the degradation of the active complement protein C3b to iC3b. Furthermore, we found that fHep-liposomes could recruit factor H and AT from human plasma. Therefore, the use of fHep-lipids could be a potential coating for liposomes and cell surfaces to regulate the immune system on the lipid surface.

Subject headings

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Keyword

Biokemi
Biochemistry

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