Probing the Hydrophobic Region of a Lipid Bilayer at Specific Depths Using Vibrational Spectroscopy

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2023 Nov 20

PMID 37982703

Authors

Md Muhaiminul Islam

Sithara U Nawagamuwage

Igor V Parshin

Margaret C Richard

Alexander L Burin

Igor V Rubtsov

Affiliations

Soon will be listed here.

Abstract

A novel spectroscopic approach for studying the flexibility and mobility in the hydrophobic interior of lipid bilayers at specific depths is proposed. A set of test compounds featuring an azido moiety and a cyano or carboxylic acid moiety, connected by an alkyl chain of different lengths, was synthesized. FTIR data and molecular dynamics calculations indicated that the test compounds in a bilayer are oriented so that the cyano or carboxylic acid moiety is located in the lipid head-group region, while the azido group stays inside the bilayer at the depth determined by its alkyl chain length. We found that the asymmetric stretching mode of the azido group (ν) can serve as a reporter of the membrane interior dynamics. FTIR and two-dimensional infrared (2DIR) studies were performed at different temperatures, ranging from 22 to 45 °C, covering the Lβ-Lα phase transition temperature of dipalmitoylphosphatidylcholine (∼41 °C). The width of the ν peak was found to be very sensitive to the phase transition and to the temperature in general. We introduced an order parameter, , which characterizes restrictions to motion inside the bilayer. 2DIR spectra of ν showed different extents of inhomogeneity at different depths in the bilayer, with the smallest inhomogeneity in the middle of the leaflet. The spectral diffusion dynamics of the N peak was found to be dependent on the depth of the N group location in the bilayer. The obtained results enhance our understanding of the bilayer dynamics and can be extended to investigate membranes with more complex compositions.

References

Oh K, Lee J, Joo C, Han H, Cho M . Beta-azidoalanine as an IR probe: application to amyloid Abeta(16-22) aggregation. J Phys Chem B. 2008; 112(33):10352-7. DOI: 10.1021/jp801558k. View

Stevenson P, Tokmakoff A . Ultrafast Fluctuations of High Amplitude Electric Fields in Lipid Membranes. J Am Chem Soc. 2017; 139(13):4743-4752. DOI: 10.1021/jacs.6b12412. View

Naumann C, Brumm T, Bayerl T . Phase transition behavior of single phosphatidylcholine bilayers on a solid spherical support studied by DSC, NMR and FT-IR. Biophys J. 2009; 63(5):1314-9. PMC: 1261435. DOI: 10.1016/S0006-3495(92)81708-3. View

Stevenson P, Tokmakoff A . Time-resolved measurements of an ion channel conformational change driven by a membrane phase transition. Proc Natl Acad Sci U S A. 2017; 114(41):10840-10845. PMC: 5642709. DOI: 10.1073/pnas.1708070114. View

Klauda J, Venable R, Freites J, OConnor J, Tobias D, Mondragon-Ramirez C . Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types. J Phys Chem B. 2010; 114(23):7830-43. PMC: 2922408. DOI: 10.1021/jp101759q. View

Venkatraman R, Baiz C . Ultrafast Dynamics at the Lipid-Water Interface: DMSO Modulates H-Bond Lifetimes. Langmuir. 2020; 36(23):6502-6511. DOI: 10.1021/acs.langmuir.0c00870. View

Kel O, Tamimi A, Fayer M . The Influence of Cholesterol on Fast Dynamics Inside of Vesicle and Planar Phospholipid Bilayers Measured with 2D IR Spectroscopy. J Phys Chem B. 2014; 119(29):8852-62. DOI: 10.1021/jp503940k. View

Seely A, Pascual J, Christou N . Science review: Cell membrane expression (connectivity) regulates neutrophil delivery, function and clearance. Crit Care. 2003; 7(4):291-307. PMC: 270693. DOI: 10.1186/cc1853. View

Mantsch H, McElhaney R . Phospholipid phase transitions in model and biological membranes as studied by infrared spectroscopy. Chem Phys Lipids. 1991; 57(2-3):213-26. DOI: 10.1016/0009-3084(91)90077-o. View

10.

Zhang Y, Lervik A, Seddon J, Bresme F . A coarse-grained molecular dynamics investigation of the phase behavior of DPPC/cholesterol mixtures. Chem Phys Lipids. 2014; 185:88-98. DOI: 10.1016/j.chemphyslip.2014.07.011. View

11.

Kel O, Tamimi A, Thielges M, Fayer M . Ultrafast structural dynamics inside planar phospholipid multibilayer model cell membranes measured with 2D IR spectroscopy. J Am Chem Soc. 2013; 135(30):11063-74. DOI: 10.1021/ja403675x. View

12.

Bristow A, Zhang T, Siemens M, Cundiff S, Mirin R . Separating homogeneous and inhomogeneous line widths of heavy- and light-hole excitons in weakly disordered semiconductor quantum wells. J Phys Chem B. 2011; 115(18):5365-71. DOI: 10.1021/jp109408s. View

13.

Kwak K, Park S, Finkelstein I, Fayer M . Frequency-frequency correlation functions and apodization in two-dimensional infrared vibrational echo spectroscopy: a new approach. J Chem Phys. 2007; 127(12):124503. DOI: 10.1063/1.2772269. View

14.

Leger J, Nyby C, Varner C, Tang J, Rubtsova N, Yue Y . Fully automated dual-frequency three-pulse-echo 2DIR spectrometer accessing spectral range from 800 to 4000 wavenumbers. Rev Sci Instrum. 2014; 85(8):083109. DOI: 10.1063/1.4892480. View

15.

Sharma V, Gupta J, Srinivasan H, Bhatt H, Garcia Sakai V, Mitra S . Curcumin Accelerates the Lateral Motion of DPPC Membranes. Langmuir. 2022; 38(31):9649-9659. DOI: 10.1021/acs.langmuir.2c01250. View

16.

Moore P, Lopez C, Klein M . Dynamical properties of a hydrated lipid bilayer from a multinanosecond molecular dynamics simulation. Biophys J. 2001; 81(5):2484-94. PMC: 1301718. DOI: 10.1016/S0006-3495(01)75894-8. View

17.

Park J, Mondal S, Kwon H, Sahu P, Han H, Kwak K . Effect of isotope substitution on the Fermi resonance and vibrational lifetime of unnatural amino acids modified with IR probe: A 2D-IR and pump-probe study of 4-azido-L-phenyl alanine. J Chem Phys. 2020; 153(16):164309. DOI: 10.1063/5.0025289. View

18.

Lee A . How lipids affect the activities of integral membrane proteins. Biochim Biophys Acta. 2004; 1666(1-2):62-87. DOI: 10.1016/j.bbamem.2004.05.012. View

19.

Redondo-Morata L, Giannotti M, Sanz F . Influence of cholesterol on the phase transition of lipid bilayers: a temperature-controlled force spectroscopy study. Langmuir. 2012; 28(35):12851-60. DOI: 10.1021/la302620t. View

20.

Kel O, Tamimi A, Fayer M . Size-dependent ultrafast structural dynamics inside phospholipid vesicle bilayers measured with 2D IR vibrational echoes. Proc Natl Acad Sci U S A. 2014; 111(3):918-23. PMC: 3903213. DOI: 10.1073/pnas.1323110111. View