Passive Internalization of Bioactive β-Casein Peptides into Phospholipid (POPC) Bilayers. Free Energy Landscapes from Unbiased Equilibrium MD Simulations at μs-Time Scale
Abstract Absorption of bioactive peptides in the intestinal epithelium take place in the apical or the basolateral tight junctions of the cells. Depending on the peptide size and hydrophobicity, translocation mechanisms involve processes of passive diffusion, active transport by pepti...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Springer US
2021
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| Online Access: | https://hdl.handle.net/1721.1/131997 |
| _version_ | 1826196307937591296 |
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| author | Jardón-Valadez, Eduardo Chen, Charles H García-Garibay, Mariano Jiménez-Guzmán, Judith Ulmschneider, Martin B |
| author2 | Massachusetts Institute of Technology. Research Laboratory of Electronics |
| author_facet | Massachusetts Institute of Technology. Research Laboratory of Electronics Jardón-Valadez, Eduardo Chen, Charles H García-Garibay, Mariano Jiménez-Guzmán, Judith Ulmschneider, Martin B |
| author_sort | Jardón-Valadez, Eduardo |
| collection | MIT |
| description | Abstract
Absorption of bioactive peptides in the intestinal epithelium take place in the apical or the basolateral tight junctions of the cells. Depending on the peptide size and hydrophobicity, translocation mechanisms involve processes of passive diffusion, active transport by peptide-cotransporters such as members of the PepT family, and transcytosis by internalization vesicles. In this work, we investigated passive diffusion of bioactive peptides of 6, 17, and 30 amino acids into lipid bilayers of (POPC) phospholipid molecules. We initially selected these three peptides because such fragments are produced by partial hydrolysis of β-casein (BCN), and because of their physiological functions: BCN6 is an agonist of opioid receptors; BCN17 is an inhibitor of thrombin and angiotensin-converting enzymes, and BCN30 promotes secretion of the protective mucin barrier in the intestine. Our computational set up consisted of unbiased equilibrium molecular dynamics simulations, at the μs-time scale, using an all-atom force field. Each peptide was allowed to freely fold and unfold, as well as enter and exit the lipid bilayer, which allows determination of peptide affinity for the bilayer interface and hydrophobic core. Passive internalization of BCN6 (YPVEPF), BCN17 (YQEPVLGPVR GPFPIIV), and BCN30 (GVSKVKEAMA PKHKEMPFPK YPVEPFTESQ) displayed different dynamics at the bilayer interface: the BCN6 peptide attached and detached throughout the simulation trajectory; BCN17 and BCN30 attached irreversibly to the bilayer interface, respectively, with N- and C-terminus fragments in close contact with lipid molecules. Quenching of tyrosine fluorescence data suggest interfacial interactions of BCN6, BCN17 and BCN30 in POPC lipid bilayers, consistent with the proposed modeling set up. This approach gave valuable information of peptide insertion and folding at a lipid bilayer, allowing to explore the initial stages of the peptide adsorption at the interface, and providing a model for evaluation of amphipathic properties of potential biofunctional peptides. |
| first_indexed | 2024-09-23T10:24:50Z |
| format | Article |
| id | mit-1721.1/131997 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:24:50Z |
| publishDate | 2021 |
| publisher | Springer US |
| record_format | dspace |
| spelling | mit-1721.1/1319972023-02-24T16:57:34Z Passive Internalization of Bioactive β-Casein Peptides into Phospholipid (POPC) Bilayers. Free Energy Landscapes from Unbiased Equilibrium MD Simulations at μs-Time Scale Jardón-Valadez, Eduardo Chen, Charles H García-Garibay, Mariano Jiménez-Guzmán, Judith Ulmschneider, Martin B Massachusetts Institute of Technology. Research Laboratory of Electronics Abstract Absorption of bioactive peptides in the intestinal epithelium take place in the apical or the basolateral tight junctions of the cells. Depending on the peptide size and hydrophobicity, translocation mechanisms involve processes of passive diffusion, active transport by peptide-cotransporters such as members of the PepT family, and transcytosis by internalization vesicles. In this work, we investigated passive diffusion of bioactive peptides of 6, 17, and 30 amino acids into lipid bilayers of (POPC) phospholipid molecules. We initially selected these three peptides because such fragments are produced by partial hydrolysis of β-casein (BCN), and because of their physiological functions: BCN6 is an agonist of opioid receptors; BCN17 is an inhibitor of thrombin and angiotensin-converting enzymes, and BCN30 promotes secretion of the protective mucin barrier in the intestine. Our computational set up consisted of unbiased equilibrium molecular dynamics simulations, at the μs-time scale, using an all-atom force field. Each peptide was allowed to freely fold and unfold, as well as enter and exit the lipid bilayer, which allows determination of peptide affinity for the bilayer interface and hydrophobic core. Passive internalization of BCN6 (YPVEPF), BCN17 (YQEPVLGPVR GPFPIIV), and BCN30 (GVSKVKEAMA PKHKEMPFPK YPVEPFTESQ) displayed different dynamics at the bilayer interface: the BCN6 peptide attached and detached throughout the simulation trajectory; BCN17 and BCN30 attached irreversibly to the bilayer interface, respectively, with N- and C-terminus fragments in close contact with lipid molecules. Quenching of tyrosine fluorescence data suggest interfacial interactions of BCN6, BCN17 and BCN30 in POPC lipid bilayers, consistent with the proposed modeling set up. This approach gave valuable information of peptide insertion and folding at a lipid bilayer, allowing to explore the initial stages of the peptide adsorption at the interface, and providing a model for evaluation of amphipathic properties of potential biofunctional peptides. 2021-09-20T17:41:20Z 2021-09-20T17:41:20Z 2020-09-30 2021-02-20T04:33:31Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/131997 en https://doi.org/10.1007/s11483-020-09651-x Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. Springer Science+Business Media, LLC, part of Springer Nature application/pdf Springer US Springer US |
| spellingShingle | Jardón-Valadez, Eduardo Chen, Charles H García-Garibay, Mariano Jiménez-Guzmán, Judith Ulmschneider, Martin B Passive Internalization of Bioactive β-Casein Peptides into Phospholipid (POPC) Bilayers. Free Energy Landscapes from Unbiased Equilibrium MD Simulations at μs-Time Scale |
| title | Passive Internalization of Bioactive β-Casein Peptides into Phospholipid (POPC) Bilayers. Free Energy Landscapes from Unbiased Equilibrium MD Simulations at μs-Time Scale |
| title_full | Passive Internalization of Bioactive β-Casein Peptides into Phospholipid (POPC) Bilayers. Free Energy Landscapes from Unbiased Equilibrium MD Simulations at μs-Time Scale |
| title_fullStr | Passive Internalization of Bioactive β-Casein Peptides into Phospholipid (POPC) Bilayers. Free Energy Landscapes from Unbiased Equilibrium MD Simulations at μs-Time Scale |
| title_full_unstemmed | Passive Internalization of Bioactive β-Casein Peptides into Phospholipid (POPC) Bilayers. Free Energy Landscapes from Unbiased Equilibrium MD Simulations at μs-Time Scale |
| title_short | Passive Internalization of Bioactive β-Casein Peptides into Phospholipid (POPC) Bilayers. Free Energy Landscapes from Unbiased Equilibrium MD Simulations at μs-Time Scale |
| title_sort | passive internalization of bioactive β casein peptides into phospholipid popc bilayers free energy landscapes from unbiased equilibrium md simulations at μs time scale |
| url | https://hdl.handle.net/1721.1/131997 |
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