Structure-Dependent Stability of Lipid-Based Polymer Amphiphiles Inserted on Erythrocytes

Cell-based therapies have the potential to transform the treatment of many diseases. One of the key challenges relating to cell therapies is to modify the cell surface with molecules to modulate cell functions such as targeting, adhesion, migration, and cell–cell interactions, or to deliver drug car...

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Main Authors: Chunsong Yu, Myunggi An, Meng Li, Charles Manke, Haipeng Liu
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Membranes
Subjects:
Online Access:https://www.mdpi.com/2077-0375/11/8/572
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author Chunsong Yu
Myunggi An
Meng Li
Charles Manke
Haipeng Liu
author_facet Chunsong Yu
Myunggi An
Meng Li
Charles Manke
Haipeng Liu
author_sort Chunsong Yu
collection DOAJ
description Cell-based therapies have the potential to transform the treatment of many diseases. One of the key challenges relating to cell therapies is to modify the cell surface with molecules to modulate cell functions such as targeting, adhesion, migration, and cell–cell interactions, or to deliver drug cargos. Noncovalent insertion of lipid-based amphiphilic molecules on the cell surface is a rapid and nontoxic approach for modifying cells with a variety of bioactive molecules without affecting the cellular functions and viability. A wide variety of lipid amphiphiles, including proteins/peptides, carbohydrates, oligonucleotides, drugs, and synthetic polymers have been designed to spontaneously anchor on the plasma membranes. These molecules typically contain a functional component, a spacer, and a long chain diacyl lipid. Though these molecular constructs appeared to be stably tethered on cell surfaces both in vitro and in vivo under static situations, their stability under mechanical stress (e.g., in the blood flow) remains unclear. Using diacyl lipid-polyethylene glycol (lipo-PEG) conjugates as model amphiphiles, here we report the effect of molecular structures on the amphiphile stability on cell surface under mechanical stress. We analyzed the retention kinetics of lipo-PEGs on erythrocytes in vitro and in vivo and found that under mechanical stress, both the molecular structures of lipid and the PEG spacer have a profound effect on the membrane retention of membrane-anchored amphiphiles. Our findings highlight the importance of molecular design on the dynamic stability of membrane-anchored amphiphiles.
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spelling doaj.art-6f43fe2ec7b048c2b370feee8ae539ec2023-11-22T08:37:37ZengMDPI AGMembranes2077-03752021-07-0111857210.3390/membranes11080572Structure-Dependent Stability of Lipid-Based Polymer Amphiphiles Inserted on ErythrocytesChunsong Yu0Myunggi An1Meng Li2Charles Manke3Haipeng Liu4Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI 48202, USADepartment of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI 48202, USADepartment of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI 48202, USADepartment of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI 48202, USADepartment of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI 48202, USACell-based therapies have the potential to transform the treatment of many diseases. One of the key challenges relating to cell therapies is to modify the cell surface with molecules to modulate cell functions such as targeting, adhesion, migration, and cell–cell interactions, or to deliver drug cargos. Noncovalent insertion of lipid-based amphiphilic molecules on the cell surface is a rapid and nontoxic approach for modifying cells with a variety of bioactive molecules without affecting the cellular functions and viability. A wide variety of lipid amphiphiles, including proteins/peptides, carbohydrates, oligonucleotides, drugs, and synthetic polymers have been designed to spontaneously anchor on the plasma membranes. These molecules typically contain a functional component, a spacer, and a long chain diacyl lipid. Though these molecular constructs appeared to be stably tethered on cell surfaces both in vitro and in vivo under static situations, their stability under mechanical stress (e.g., in the blood flow) remains unclear. Using diacyl lipid-polyethylene glycol (lipo-PEG) conjugates as model amphiphiles, here we report the effect of molecular structures on the amphiphile stability on cell surface under mechanical stress. We analyzed the retention kinetics of lipo-PEGs on erythrocytes in vitro and in vivo and found that under mechanical stress, both the molecular structures of lipid and the PEG spacer have a profound effect on the membrane retention of membrane-anchored amphiphiles. Our findings highlight the importance of molecular design on the dynamic stability of membrane-anchored amphiphiles.https://www.mdpi.com/2077-0375/11/8/572erythrocytesmembranesamphiphileslipid
spellingShingle Chunsong Yu
Myunggi An
Meng Li
Charles Manke
Haipeng Liu
Structure-Dependent Stability of Lipid-Based Polymer Amphiphiles Inserted on Erythrocytes
Membranes
erythrocytes
membranes
amphiphiles
lipid
title Structure-Dependent Stability of Lipid-Based Polymer Amphiphiles Inserted on Erythrocytes
title_full Structure-Dependent Stability of Lipid-Based Polymer Amphiphiles Inserted on Erythrocytes
title_fullStr Structure-Dependent Stability of Lipid-Based Polymer Amphiphiles Inserted on Erythrocytes
title_full_unstemmed Structure-Dependent Stability of Lipid-Based Polymer Amphiphiles Inserted on Erythrocytes
title_short Structure-Dependent Stability of Lipid-Based Polymer Amphiphiles Inserted on Erythrocytes
title_sort structure dependent stability of lipid based polymer amphiphiles inserted on erythrocytes
topic erythrocytes
membranes
amphiphiles
lipid
url https://www.mdpi.com/2077-0375/11/8/572
work_keys_str_mv AT chunsongyu structuredependentstabilityoflipidbasedpolymeramphiphilesinsertedonerythrocytes
AT myunggian structuredependentstabilityoflipidbasedpolymeramphiphilesinsertedonerythrocytes
AT mengli structuredependentstabilityoflipidbasedpolymeramphiphilesinsertedonerythrocytes
AT charlesmanke structuredependentstabilityoflipidbasedpolymeramphiphilesinsertedonerythrocytes
AT haipengliu structuredependentstabilityoflipidbasedpolymeramphiphilesinsertedonerythrocytes