Binding of Alpha-Crystallin to Cortical and Nuclear Lens Lipid Membranes Derived from a Single Lens

Timsina, Raju; Wellisch, Samantha; Haemmerle, Dieter; Mainali, Laxman

doi:10.3390/ijms231911295

Cited by 4 publications

(27 citation statements)

References 133 publications

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“…Using continuous wave EPR spin labeling and SUVs as a membrane model, Mainali’s group showed that high Chol content and the presence of CBDs inhibits the binding of α-crystallin to membranes made of the major PLs of the eye lens fiber cell plasma membranes. They showed that the same conclusion is valid for membranes (SUV) made of the total lipids extracted from bovine cortical and nuclear lenses [ 97 ]. These results present another mechanism through which high Chol and CBDs protect the eye lens against age-related cataract development.…”

Section: Understanding Of Cbd Functions In Model Membranes Helps To U...mentioning

confidence: 87%

Membrane Models and Experiments Suitable for Studies of the Cholesterol Bilayer Domains

et al. 2023

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Cholesterol (Chol) is an essential component of animal cell membranes and is most abundant in plasma membranes (PMs) where its concentration typically ranges from 10 to 30 mol%. However, in red blood cells and Schwann cells, PMs Chol content is as high as 50 mol%, and in the PMs of the eye lens fiber cells, it can reach up to 66 mol%. Being amphiphilic, Chol molecules are easily incorporated into the lipid bilayer where they affect the membrane lateral organization and transmembrane physical properties. In the aqueous phase, Chol cannot form free bilayers by itself. However, pure Chol bilayer domains (CBDs) can form in lipid bilayer membranes with the Chol content exceeding 50 mol%. The range of Chol concentrations surpassing 50 mol% is less frequent in biological membranes and is consequently less investigated. Nevertheless, it is significant for the normal functioning of the eye lens and understanding how Chol plaques form in atherosclerosis. The most commonly used membrane models are unilamellar and multilamellar vesicles (MLVs) and supported lipid bilayers (SLBs). CBDs have been observed directly using confocal microscopy, X-ray reflectometry and saturation recovery electron paramagnetic resonance (SR EPR). Indirect evidence of CBDs has also been reported by using atomic force microscopy (AFM) and fluorescence recovery after photobleaching (FRAP) experiments. The overall goal of this review is to demonstrate the advantages and limitations of the various membrane models and experimental techniques suitable for the detection and investigation of the lateral organization, function and physical properties of CBDs.

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Section: Understanding Of Cbd Functions In Model Membranes Helps To U...mentioning

confidence: 87%

Membrane Models and Experiments Suitable for Studies of the Cholesterol Bilayer Domains

et al. 2023

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“…Additional studies of α-crystallin in Chol-containing lipid membranes showed that both the membrane lipid and Chol composition strongly affects the membrane interactions of α-crystallin and the physical membrane properties [67,70]. Our most recent studies on α-crystallin interactions with isolated bovine lens cortical and nuclear total lipids showed α-crystallin binds to both the CM and NM but has significantly higher binding in the NM due to the variations in lipid and Chol composition between the lens regions [75]. Ultimately, these studies show α-crystallin binds to the lens lipid membrane and is strongly modulated by the lens membrane lipid and Chol composition.…”

Section: Introductionmentioning

confidence: 90%

“…Moreover, the 68 yo female donor with the highest MSO by α-crystallin in the CM was a long-term smoker, pre-diabetic, and had hypertension, which have all been associated with increasing oxidative stress and the development of cataracts [77][78][79][80][81][82][83][84][85][86]. As oxidative stress has been shown to likely reduce the lens Chol composition [35,[44][45][46][47][48], and reduced Chol is shown to lead to a diminished number and size of CBDs in CM and NM [43], the development of cataracts [50], and allow for increased α-crystallin binding [67,70,75], a reduction in Chol and CBDs content is likely why the highest MSO is seen in this donor. Therefore, in unison with gender-related risks, these health conditions will likely reduce the Chol and CBD content and allow for increased membrane binding with an increase in cataract grade.…”

Section: Mso By α-Crystallin In Individual Eye Lens Cortical and Nucl...mentioning

confidence: 99%

“…Moreover, the change between CMs with a grade of one CC grade separation is largest with the initial development of cataracts, but the relative difference decreases with the progression of CC. This lessening in trend may be due to the reduction in Chol content shown to occur with the progression of cataracts, as a reduction in Chol is shown to cause an increase in mobility near the membrane surface [70,71,75,113], alleviating the decrease in mobility seen from the increase in SM content. Conversely, the change between α-crystallin absent controls of the NM did not follow the trend seen in the CM, showing a slight but non-significant increase with cataract development, resulting in lower levels of SM than in the CM, and the decrease in Chol content in cataractous lenses is significantly larger in the NM than in the CM [43,114,115].…”

Section: Membrane Mobility On the Surface Of Individual Eye Lens Cort...mentioning

confidence: 99%

“…To the best of our knowledge, previous studies of α-crystallin binding to lens lipid membranes were performed either with only CMs [51,54,62,72], total lens lipid extracted from the whole lens [52,63,69,74], or contained intrinsic membrane proteins [54,63,69]. Moreover, we have recently studied the binding of α-crystallin in bovine CM and NM with lipids derived from a single lens [75], but no studies have been conducted on the binding of α-crystallin in separate human CM and NM derived from a single lens.…”

Section: Introductionmentioning

confidence: 99%

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Association of Alpha-Crystallin with Human Cortical and Nuclear Lens Lipid Membrane Increases with the Grade of Cortical and Nuclear Cataract

Hazen,

Trossi-Torres,

Timsina

et al. 2024

IJMS

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Eye lens α-crystallin has been shown to become increasingly membrane-bound with age and cataract formation; however, to our knowledge, no studies have investigated the membrane interactions of α-crystallin throughout the development of cataracts in separated cortical membrane (CM) and nuclear membrane (NM) from single human lenses. In this study, four pairs of human lenses from age-matched male and female donors and one pair of male lenses ranging in age from 64 to 73 years old (yo) were obtained to investigate the interactions of α-crystallin with the NM and CM throughout the progression of cortical cataract (CC) and nuclear cataract (NC) using the electron paramagnetic resonance spin-labeling method. Donor health history information (diabetes, smoker, hypertension, radiation treatment), sex, and race were included in the data analysis. The right eye lenses CM and NM investigated were 64 yo male (CC: 0), 68 yo male (CC: 3, NC: 2), 73 yo male (CC: 1, NC: 2), 68 yo female (CC: 3, NC: 2), and 73 yo female (CC: 1, NC: 3). Similarly, left eye lenses CM and NM investigated were 64 yo male (CC: 0), 68 yo male (CC: 3, NC: 2), 73 yo male (CC: 2, NC: 3), 68 yo female (CC: 3, NC: 2), and 73 yo female (CC: 1, NC: 3). Analysis of α-crystallin binding to male and female eye lens CM and NM revealed that the percentage of membrane surface occupied (MSO) by α-crystallin increases with increasing grade of CC and NC. The binding of α-crystallin resulted in decreased mobility, increased order, and increased hydrophobicity on the membrane surface in male and female eye lens CM and NM. CM mobility decreased with an increase in cataracts for both males and females, whereas the male lens NM mobility showed no significant change, while female lens NM showed increased mobility with an increase in cataract grade. Our data shows that a 68 yo female donor (long-term smoker, pre-diabetic, and hypertension; grade 3 CC) showed the largest MSO by α-crystallin in CM from both the left and right lens and had the most pronounced mobility changes relative to all other analyzed samples. The variation in cholesterol (Chol) content, size and amount of cholesterol bilayer domains (CBDs), and lipid composition in the CM and NM with age and cataract might result in a variation of membrane surface mobility, membrane surface hydrophobicity, and the interactions of α-crystallin at the surface of each CM and NM. These findings provide insight into the effect of decreased Chol content and the reduced size and amount of CBDs in the cataractous CM and NM with an increased binding of α-crystallin with increased CC and NC grade, which suggests that Chol and CBDs might be a key component in maintaining lens transparency.

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Binding of βL-Crystallin with Models of Animal and Human Eye Lens-Lipid Membrane

Hazen,

Trossi-Torres,

Khadka

et al. 2023

IJMS

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Several discoveries show that with age and cataract formation, β-crystallin binds with the lens membrane or associates with other lens proteins, which bind with the fiber cell plasma membrane, accompanied by light scattering and cataract formation. However, how lipids (phospholipids and sphingolipids) and cholesterol (Chol) influence β-crystallin binding to the membrane is unclear. This research aims to elucidate the role of lipids and Chol in the binding of β-crystallin to the membrane and the membrane’s physical properties (mobility, order, and hydrophobicity) with β-crystallin binding. We used electron paramagnetic resonance (EPR) spin-labeling methods to investigate the binding of βL-crystallin with a model of porcine lens-lipid (MPLL), model of mouse lens-lipid (MMLL), and model of human lens-lipid (MHLL) membrane with and without Chol. Our results show that βL-crystallin binds with all of the investigated membranes in a saturation manner, and the maximum parentage of the membrane surface occupied (MMSO) by βL-crystallin and the binding affinity (Ka) of βL-crystallin to the membranes followed trends: MMSO (MPLL) > MMSO (MMLL) > MMSO (MHLL) and Ka (MHLL) > Ka (MMLL) ≈ Ka (MPLL), respectively, in which the presence of Chol reduces the MMSO and Ka for all membranes. The mobility near the headgroup regions of the membranes decreases with an increase in the binding of βL-crystallin; however, the decrease is more pronounced in the MPLL and MMLL membranes than the MHLL membrane. In the MPLL and MMLL membranes, the membranes become slightly ordered near the headgroup with an increase in βL-crystallin binding compared to the MHLL membrane. The hydrophobicity near the headgroup region of the membrane increases with βL-crystallin binding; however, the increase is more pronounced in the MPLL and MMLL membranes than the MHLL membrane, indicating that βL-crystallin binding creates a hydrophobic barrier for the passage of polar molecules, which supports the barrier hypothesis in cataract formation. However, in the presence of Chol, there is no significant increase in hydrophobicity with βL-crystallin binding, suggesting that Chol prevents the formation of a hydrophobic barrier, possibly protecting against cataract formation.

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Binding of Alpha-Crystallin to Cortical and Nuclear Lens Lipid Membranes Derived from a Single Lens

Cited by 4 publications

References 133 publications

Membrane Models and Experiments Suitable for Studies of the Cholesterol Bilayer Domains

Membrane Models and Experiments Suitable for Studies of the Cholesterol Bilayer Domains

Association of Alpha-Crystallin with Human Cortical and Nuclear Lens Lipid Membrane Increases with the Grade of Cortical and Nuclear Cataract

Binding of βL-Crystallin with Models of Animal and Human Eye Lens-Lipid Membrane

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