Insights into the behavioral difference of water in the presence of GM1

Basu, Ipsita; Manna, Moutusi; Mukhopadhyay, Chaitali

doi:10.1016/j.febslet.2015.11.014

Cited by 2 publications

(2 citation statements)

References 78 publications

(83 reference statements)

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“…To elucidate the source of enhanced Coulombic interaction, the electrostatic potential for the contact monolayer surface of the lipid bilayer in two cases was computed (Figure c,d). The electrostatics calculations were done using adaptive Poisson Boltzmann solver module in VMD .…”

Section: Resultsmentioning

confidence: 99%

Insight into the Mechanism of Carrier-Mediated Delivery of siRNA in the Cell Membrane Using MD Simulation

Basu

Maiti

2020

Langmuir

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The effective translocation of small interfering RNA (siRNA) across cell membranes has become one of the main challenges in gene silencing therapy. In this study, we have carried out molecular dynamics simulations to investigate a systematic procedure with different carriers that could be convenient for efficient siRNA delivery into the cell. Starting with poly-amidoamine (PAMAM) dendrimers and cholesterol molecules as carriers, we have found cholesterol as the most efficient carrier for siRNA when it is covalently attached with the siRNA terminal group. Our simulations show that binding of this complex in the lipid membrane alters the structure and dynamics of the nearby lipids to initiate the translocation process. Potential of mean force (PMF) was computed for siRNA with the carriers along the bilayer normal to understand the spontaneity of the process. Though all the PMF profiles show repulsive interaction inside the bilayer, the siRNA with cholesterol shows a comparative attractive interaction (∼27 kcal/mol) with respect to the siRNA−PAMAM complex. Altogether, our results demonstrate the binding interaction of the siRNA−carrier complex in the lipid membrane and propose a theoretical model for the efficient carrier by comparative study of the binding. The probable mechanism of the translocation process is also provided by the alteration of the lipid structure and dynamics for specifically siRNA−cholesterol binding.

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Section: Resultsmentioning

confidence: 99%

Insight into the Mechanism of Carrier-Mediated Delivery of siRNA in the Cell Membrane Using MD Simulation

Basu

Maiti

2020

Langmuir

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“…These results are also in accordance with a recent publication suggesting that the presence of GM1 in mixed micelle systems increases the confined region up to 16 Å for diffusible water, which is evident in both of the independent simulation systems for POPC:POPG:cholesterol:GM1. 55 Overall, the lipid bilayer thickness appears to be more perturbed by KK13 when it is composed of a single lipid while the mixed bilayer is less affected. Similar analysis of the micelle perturbation by KK13 was not possible since the uniformity of head groups was not maintained throughout MD simulation (Fig.…”

Section: Disruption Of Membrane Integrity By Kk13 Bindingmentioning

confidence: 95%

Biophysical insights into the membrane interaction of the core amyloid-forming Aβ₄₀fragment K16–K28 and its role in the pathogenesis of Alzheimer's disease

Bera

Korshavn

Kar

et al. 2016

Phys. Chem. Chem. Phys.

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The aggregation of amyloid-β (Aβ) on neuronal membranes is implicated in both neuronal toxicity and the progression of Alzheimer's disease. Unfortunately, the heterogeneous environment that results from peptide aggregation in the presence of lipids makes the details of these pathways difficult to interrogate. In this study, we report an investigation of the membrane interaction of an Aβ fragment (K16LVFFAEDVGSNK28, KK13), which maintains the amyloidogenic nature of the full-length peptide and is implicated in membrane-mediated folding, through a combination of NMR spectroscopy and molecular dynamics simulations. Despite KK13's ability to form amyloids in solution, the monomer remains unstructured in the presence of lipid bilayers, unlike its full-length parent peptide. Additionally, NMR and molecular dynamics simulation results support that the presence of GM1 ganglioside, a lipid which strongly promotes binding between Aβ and lipid bilayers, promotes KK13 binding to but not folding on the membrane. Finally, we show that the peptide partitions between the membrane and aqueous solution based on the hydrophobicity of the N-terminal residues, regardless of lipid composition. These results support previous discoveries suggesting the importance of GM1 ganglioside in exacerbating membrane-driven aggregation while identifying the potential importance of C-terminal residues in membrane binding and folding, which has previously been unclear.

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Insights into the behavioral difference of water in the presence of GM1

Cited by 2 publications

References 78 publications

Insight into the Mechanism of Carrier-Mediated Delivery of siRNA in the Cell Membrane Using MD Simulation

Insight into the Mechanism of Carrier-Mediated Delivery of siRNA in the Cell Membrane Using MD Simulation

Biophysical insights into the membrane interaction of the core amyloid-forming Aβ₄₀fragment K16–K28 and its role in the pathogenesis of Alzheimer's disease

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Insights into the behavioral difference of water in the presence of GM1

Cited by 2 publications

References 78 publications

Insight into the Mechanism of Carrier-Mediated Delivery of siRNA in the Cell Membrane Using MD Simulation

Insight into the Mechanism of Carrier-Mediated Delivery of siRNA in the Cell Membrane Using MD Simulation

Biophysical insights into the membrane interaction of the core amyloid-forming Aβ40fragment K16–K28 and its role in the pathogenesis of Alzheimer's disease

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Biophysical insights into the membrane interaction of the core amyloid-forming Aβ₄₀fragment K16–K28 and its role in the pathogenesis of Alzheimer's disease