Lipid Membrane Remodeling by the Micellar Aggregation of Long-Chain Unsaturated Fatty Acids for Sustainable Antimicrobial Strategies
Antimicrobial fatty acids derived from natural sources and renewable feedstocks are promising surface-active substances with a wide range of applications. Their ability to target bacterial membrane in multiple mechanisms offers a promising antimicrobial approach for combating bacterial infections an...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/11/9639 |
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| author | Sungmin Shin Hyunhyuk Tae Soohyun Park Nam-Joon Cho |
| author_facet | Sungmin Shin Hyunhyuk Tae Soohyun Park Nam-Joon Cho |
| author_sort | Sungmin Shin |
| collection | DOAJ |
| description | Antimicrobial fatty acids derived from natural sources and renewable feedstocks are promising surface-active substances with a wide range of applications. Their ability to target bacterial membrane in multiple mechanisms offers a promising antimicrobial approach for combating bacterial infections and preventing the development of drug-resistant strains, and it provides a sustainable strategy that aligns with growing environmental awareness compared to their synthetic counterparts. However, the interaction and destabilization of bacterial cell membranes by these amphiphilic compounds are not yet fully understood. Here, we investigated the concentration-dependent and time-dependent membrane interaction between long-chain unsaturated fatty acids—linolenic acid (LNA, C18:3), linoleic (LLA, C18:2), and oleic acid (OA, C18:1)—and the supported lipid bilayers (SLBs) using quartz crystal microbalance-dissipation (QCM-D) and fluorescence microscopy. We first determined the critical micelle concentration (CMC) of each compound using a fluorescence spectrophotometer and monitored the membrane interaction in real time following fatty acid treatment, whereby all micellar fatty acids elicited membrane-active behavior primarily above their respective CMC values. Specifically, LNA and LLA, which have higher degrees of unsaturation and CMC values of 160 µM and 60 µM, respectively, caused significant changes in the membrane with net |Δ<i>f</i>| shifts of 23.2 ± 0.8 Hz and 21.4 ± 0.6 Hz and Δ<i>D</i> shifts of 5.2 ± 0.5 × 10<sup>−6</sup> and 7.4 ± 0.5 × 10<sup>−6</sup>. On the other hand, OA, with the lowest unsaturation degree and CMC value of 20 µM, produced relatively less membrane change with a net |Δ<i>f</i>| shift of 14.6 ± 2.2 Hz and Δ<i>D</i> shift of 8.8 ± 0.2 × 10<sup>−6</sup>. Both LNA and LLA required higher concentrations than OA to initiate membrane remodeling as their CMC values increased with the degree of unsaturation. Upon incubating with fluorescence-labeled model membranes, the fatty acids induced tubular morphological changes at concentrations above CMC. Taken together, our findings highlight the critical role of self-aggregation properties and the degree of unsaturated bonds in unsaturated long-chain fatty acids upon modulating membrane destabilization, suggesting potential applications in developing sustainable and effective antimicrobial strategies. |
| first_indexed | 2024-03-11T03:04:52Z |
| format | Article |
| id | doaj.art-9e39e165a662407a9680cae4d4cb6c83 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:04:52Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9e39e165a662407a9680cae4d4cb6c832023-11-18T08:01:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-012411963910.3390/ijms24119639Lipid Membrane Remodeling by the Micellar Aggregation of Long-Chain Unsaturated Fatty Acids for Sustainable Antimicrobial StrategiesSungmin Shin0Hyunhyuk Tae1Soohyun Park2Nam-Joon Cho3School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, SingaporeSchool of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, SingaporeSchool of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, SingaporeSchool of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, SingaporeAntimicrobial fatty acids derived from natural sources and renewable feedstocks are promising surface-active substances with a wide range of applications. Their ability to target bacterial membrane in multiple mechanisms offers a promising antimicrobial approach for combating bacterial infections and preventing the development of drug-resistant strains, and it provides a sustainable strategy that aligns with growing environmental awareness compared to their synthetic counterparts. However, the interaction and destabilization of bacterial cell membranes by these amphiphilic compounds are not yet fully understood. Here, we investigated the concentration-dependent and time-dependent membrane interaction between long-chain unsaturated fatty acids—linolenic acid (LNA, C18:3), linoleic (LLA, C18:2), and oleic acid (OA, C18:1)—and the supported lipid bilayers (SLBs) using quartz crystal microbalance-dissipation (QCM-D) and fluorescence microscopy. We first determined the critical micelle concentration (CMC) of each compound using a fluorescence spectrophotometer and monitored the membrane interaction in real time following fatty acid treatment, whereby all micellar fatty acids elicited membrane-active behavior primarily above their respective CMC values. Specifically, LNA and LLA, which have higher degrees of unsaturation and CMC values of 160 µM and 60 µM, respectively, caused significant changes in the membrane with net |Δ<i>f</i>| shifts of 23.2 ± 0.8 Hz and 21.4 ± 0.6 Hz and Δ<i>D</i> shifts of 5.2 ± 0.5 × 10<sup>−6</sup> and 7.4 ± 0.5 × 10<sup>−6</sup>. On the other hand, OA, with the lowest unsaturation degree and CMC value of 20 µM, produced relatively less membrane change with a net |Δ<i>f</i>| shift of 14.6 ± 2.2 Hz and Δ<i>D</i> shift of 8.8 ± 0.2 × 10<sup>−6</sup>. Both LNA and LLA required higher concentrations than OA to initiate membrane remodeling as their CMC values increased with the degree of unsaturation. Upon incubating with fluorescence-labeled model membranes, the fatty acids induced tubular morphological changes at concentrations above CMC. Taken together, our findings highlight the critical role of self-aggregation properties and the degree of unsaturated bonds in unsaturated long-chain fatty acids upon modulating membrane destabilization, suggesting potential applications in developing sustainable and effective antimicrobial strategies.https://www.mdpi.com/1422-0067/24/11/9639antimicrobial lipidlong-chain unsaturated fatty acidantibacteriallipid bilayer membranequartz crystal microbalance–dissipationmodel membrane system |
| spellingShingle | Sungmin Shin Hyunhyuk Tae Soohyun Park Nam-Joon Cho Lipid Membrane Remodeling by the Micellar Aggregation of Long-Chain Unsaturated Fatty Acids for Sustainable Antimicrobial Strategies International Journal of Molecular Sciences antimicrobial lipid long-chain unsaturated fatty acid antibacterial lipid bilayer membrane quartz crystal microbalance–dissipation model membrane system |
| title | Lipid Membrane Remodeling by the Micellar Aggregation of Long-Chain Unsaturated Fatty Acids for Sustainable Antimicrobial Strategies |
| title_full | Lipid Membrane Remodeling by the Micellar Aggregation of Long-Chain Unsaturated Fatty Acids for Sustainable Antimicrobial Strategies |
| title_fullStr | Lipid Membrane Remodeling by the Micellar Aggregation of Long-Chain Unsaturated Fatty Acids for Sustainable Antimicrobial Strategies |
| title_full_unstemmed | Lipid Membrane Remodeling by the Micellar Aggregation of Long-Chain Unsaturated Fatty Acids for Sustainable Antimicrobial Strategies |
| title_short | Lipid Membrane Remodeling by the Micellar Aggregation of Long-Chain Unsaturated Fatty Acids for Sustainable Antimicrobial Strategies |
| title_sort | lipid membrane remodeling by the micellar aggregation of long chain unsaturated fatty acids for sustainable antimicrobial strategies |
| topic | antimicrobial lipid long-chain unsaturated fatty acid antibacterial lipid bilayer membrane quartz crystal microbalance–dissipation model membrane system |
| url | https://www.mdpi.com/1422-0067/24/11/9639 |
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