Tethered Bilayer Lipid Membranes to Monitor Heat Transfer between Gold Nanoparticles and Lipid Membranes

Alghalayini, Amani; Jiang, Lele; Gu, Xi; Yeoh, Guan Heng; Cranfield, Charles G.; Timchenko, Victoria; Cornell, Bruce; Valenzuela, Stella M.

doi:10.3791/61851

Cited by 3 publications

(3 citation statements)

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“…Prior to experiment, a monolayer of anchor lipids was covalently attached to the gold electrode surface via gold-sulfur dative bonding and the anchor lipid mixture consisted of anchor lipids possessing a tether unit that binds the lipid to the solid support and an exposed hydrophobic lipid part that acts as the bottom leaflet of the tethered lipid bilayer, along with a spacer moiety that separates the tether units laterally [ 39 ]. The monolayer was formed by incubating an ethanolic solution of dissolved tether and spacer molecules in a 9:1 molar ratio with the gold electrode surface, followed by ethanol rinsing [ 38 ]. Afterwards, the complete lipid bilayer architecture of the tBLM platform was formed by incubating the monolayer-functionalized gold electrode surface with an ethanolic solution of dissolved 70% zwitterionic C20 diphytanyl-diether-phosphatidylcholine lipid and 30% C20 glycerol diphytanyl ether (DPEPC) lipid.…”

Section: Resultsmentioning

confidence: 99%

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Mechanistic Evaluation of Antimicrobial Lipid Interactions with Tethered Lipid Bilayers by Electrochemical Impedance Spectroscopy

Tan

Jeon

Yoon

et al. 2022

Sensors

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There is extensive interest in developing real-time biosensing strategies to characterize the membrane-disruptive properties of antimicrobial lipids and surfactants. Currently used biosensing strategies mainly focus on tracking membrane morphological changes such as budding and tubule formation, while there is an outstanding need to develop a label-free biosensing strategy to directly evaluate the molecular-level mechanistic details by which antimicrobial lipids and surfactants disrupt lipid membranes. Herein, using electrochemical impedance spectroscopy (EIS), we conducted label-free biosensing measurements to track the real-time interactions between three representative compounds—glycerol monolaurate (GML), lauric acid (LA), and sodium dodecyl sulfate (SDS)—and a tethered bilayer lipid membrane (tBLM) platform. The EIS measurements verified that all three compounds are mainly active above their respective critical micelle concentration (CMC) values, while also revealing that GML induces irreversible membrane damage whereas the membrane-disruptive effects of LA are largely reversible. In addition, SDS micelles caused membrane solubilization, while SDS monomers still caused membrane defect formation, shedding light on how antimicrobial lipids and surfactants can be active in, not only micellar form, but also as monomers in some cases. These findings expand our mechanistic knowledge of how antimicrobial lipids and surfactants disrupt lipid membranes and demonstrate the analytical merits of utilizing the EIS sensing approach to comparatively evaluate membrane-disruptive antimicrobial compounds.

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Section: Resultsmentioning

confidence: 99%

“…All EIS measurements were performed in alternating current (AC) mode, and swept-frequency impedance spectroscopy with a 25 mV AC excitation (see also refs. [ 28 , 37 , 38 ]) and frequency range of 0.1 Hz to 2000 Hz was used. No offset voltage was applied.…”

Section: Methodsmentioning

confidence: 99%

Mechanistic Evaluation of Antimicrobial Lipid Interactions with Tethered Lipid Bilayers by Electrochemical Impedance Spectroscopy

Tan

Jeon

Yoon

et al. 2022

Sensors

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“…However, whether these chemotherapeutic drugs may finally lead to cancer recurrence remain unknown [ 4 ]. In this case, some external stimulus means such as heat [ 5 ], light [ 6 ], magnetism [ 7 , 8 ], and ultrasound (US) [ 9 ] have been investigated to aid topical drug administration, and they are all practicable for clinical and research applications. US is typically used to stimulate sound-sensitive agents (sonosensitizers) to exert cytotoxic effects, a process referred to as sonodynamic therapy (SDT).…”

Section: Introductionmentioning

confidence: 99%

Mechanism-Based Sonodynamic–Chemo Combinations against Triple-Negative Breast Cancer

Feng

Chen

Yang

et al. 2022

IJMS

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Due to its noninvasive nature, site-confined irradiation, and high tissue penetrating capabilities, ultrasound (US)-driven sonodynamic treatment (SDT) has been proven to have broad application possibilities in neoplastic and non-neoplastic diseases. However, the inefficient buildup of sonosensitizers in the tumor site remarkably impairs SDT efficiency. The present work proposes a deep-penetrating sonochemistry nanoplatform (Pp18-lipos@SRA737&DOX, PSDL) comprising Pp18 liposomes (Pp18-lipos, Plipo), SRA737 (a CHK1 inhibitor), and doxorubicin (DOX) for the controlled formation of reactive oxygen species (ROS) and release of DOX and SRA737 upon US activation, therefore increasing chemotherapeutic effectiveness and boosting SDT efficacy. Therein, the antitumor activities of DOX have been attributed to its intercalation into the nucleus DNA and induction of cell apoptosis. CHK1 evolved to respond to DNA damage and repair the damage via cell cycle progression. SRA737 is a potent and orally bioavailable clinical drug candidate for inhibiting CHK1, demonstrating adjuvant anticancer effect in vitro and in vivo. It was interesting to find that SRA737 carried into Plipo@DOX could significantly alleviate G2/M cell cycle arrest and aggravate DNA double-strand injuries, resulting in significant cell death. The developed US-switchable nanosystem provides a promising strategy for augmenting sono-chemotherapy against breast cancer controllably and precisely.

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Biophysical Characterization of LTX-315 Anticancer Peptide Interactions with Model Membrane Platforms: Effect of Membrane Surface Charge

Koo

Sut

Tan

et al. 2022

IJMS

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LTX-315 is a clinical-stage, anticancer peptide therapeutic that disrupts cancer cell membranes. Existing mechanistic knowledge about LTX-315 has been obtained from cell-based biological assays, and there is an outstanding need to directly characterize the corresponding membrane-peptide interactions from a biophysical perspective. Herein, we investigated the membrane-disruptive properties of the LTX-315 peptide using three cell-membrane-mimicking membrane platforms on solid supports, namely the supported lipid bilayer, intact vesicle adlayer, and tethered lipid bilayer, in combination with quartz crystal microbalance-dissipation (QCM-D) and electrochemical impedance spectroscopy (EIS) measurements. The results showed that the cationic LTX-315 peptide selectively disrupted negatively charged phospholipid membranes to a greater extent than zwitterionic or positively charged phospholipid membranes, whereby electrostatic interactions were the main factor to influence peptide attachment and membrane curvature was a secondary factor. Of note, the EIS measurements showed that the LTX-315 peptide extensively and irreversibly permeabilized negatively charged, tethered lipid bilayers that contained high phosphatidylserine lipid levels representative of the outer leaflet of cancer cell membranes, while circular dichroism (CD) spectroscopy experiments indicated that the LTX-315 peptide was structureless and the corresponding membrane-disruptive interactions did not involve peptide conformational changes. Dynamic light scattering (DLS) measurements further verified that the LTX-315 peptide selectively caused irreversible disruption of negatively charged lipid vesicles. Together, our findings demonstrate that the LTX-315 peptide preferentially disrupts negatively charged phospholipid membranes in an irreversible manner, which reinforces its potential as an emerging cancer immunotherapy and offers a biophysical framework to guide future peptide engineering efforts.

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Tethered Bilayer Lipid Membranes to Monitor Heat Transfer between Gold Nanoparticles and Lipid Membranes

Cited by 3 publications

References 0 publications

Mechanistic Evaluation of Antimicrobial Lipid Interactions with Tethered Lipid Bilayers by Electrochemical Impedance Spectroscopy

Mechanistic Evaluation of Antimicrobial Lipid Interactions with Tethered Lipid Bilayers by Electrochemical Impedance Spectroscopy

Mechanism-Based Sonodynamic–Chemo Combinations against Triple-Negative Breast Cancer

Biophysical Characterization of LTX-315 Anticancer Peptide Interactions with Model Membrane Platforms: Effect of Membrane Surface Charge

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