The adhesion modes and endocytosis pathway of spherocylindrical nanoparticles (NPs) are investigated numerically using molecular dynamics simulations of a coarse-grained implicit-solvent model. The investigation is performed systematically with respect to the adhesion energy density ξ, NP’s diameter D, and NP’s aspect ratio α. At weak ξ, the NP adheres to the membrane through a parallel mode, i.e., its principal axis is parallel to the membrane. However, for relatively large ξ, the NP adheres through a perpendicular mode, i.e., the NP is invaginated, such as its principal axis is nearly perpendicular to the membrane. The value of ξ at the transition from the parallel to the perpendicular mode decreases with increasing the D or α, in agreement with theoretical arguments based on the Helfrich Hamiltonian. As ξ is further increased, the NP undergoes endocytosis, with the value of ξ at the endocytosis threshold that is independent of the aspect ratio but decreases with increasing D. The kinetics of endocytosis depends strongly on ξ and D. While for low values of D, the NP first rotates to a parallel orientation then to a perpendicular orientation. At high values of ξ or D, the NP is endocytosed while in the parallel orientation.
more »
« less
Membrane-mediated dimerization of spherocylindrical nanoparticles
We present a numerical investigation of the modes of adhesion and endocytosis of two spherocylindrical nanoparticles (SCNPs) on planar and tensionless lipid membranes, using systematic molecular dynamics simulations of an implicit-solvent model, with varying values of the SCNPs' adhesion strength and dimensions. We found that at weak values of the adhesion energy per unit of area, ξ , the SCNPs are monomeric and adhere to the membrane in the parallel mode. As ξ is slightly increased, the SCNPs dimerize into wedged dimers, with an obtuse angle between their major axes that decreases with increasing ξ . However, as ξ is further increased, we found that the final adhesion state of the two SCNPs is strongly affected by the initial distance, d 0 , between their centers of mass, upon their adhesion. Namely, the SCNPs dimerize into wedged dimers, with an acute angle between their major axes, if d 0 is relatively small. However, for relatively high d 0 , they adhere individually to the membrane in the monomeric normal mode. For even higher values of ξ and small values of d 0 , the SCNPs cluster into tubular dimers. However, they remain monomeric if d 0 is high. Finally, the SCNPs endocytose either as a tubular dimer, if d 0 is low or as monomers for large d 0 , with the onset value of ξ of dimeric endocytosis being lower than that of monomeric endocytosis. Dimeric endocytosis requires that the SCNPs adhere simultaneously at nearby locations.
more »
« less
- Award ID(s):
- 1931837
- NSF-PAR ID:
- 10399415
- Date Published:
- Journal Name:
- Soft Matter
- Volume:
- 19
- Issue:
- 8
- ISSN:
- 1744-683X
- Page Range / eLocation ID:
- 1499 to 1512
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
null (Ed.)Using molecular dynamics simulations of a coarse-grained implicit solvent model, we investigate the binding of crescent-shaped nanoparticles (NPs) on tubular lipid membranes. The NPs adhere to the membrane through their concave side. We found that the binding/unbinding transition is first-order, with the threshold binding energy being higher than the unbinding threshold, and the energy barrier between the bound and unbound states at the transition that increases with increasing the NP's arclength L np or curvature mismatch μ = R c / R np , where R c and R np are the radii of curvature of the tubular membrane and the NP, respectively. Furthermore, we found that the threshold binding energy increases with increasing either L np or μ . NPs with curvature larger than that of the tubule ( μ > 1) lie perpendicularly to the tubule's axis. However, for μ smaller than a specific arclength-dependent mismatch μ *, the NPs are tilted with respect to the tubule's axis, with the tilt angle that increases with decreasing μ . We also investigated the self-assembly of the NPs on the tubule at relatively weak adhesion strength and found that for μ > 1 and high values of L np , the NPs self-assemble into linear chains, and lie side-by-side. For μ < μ * and high L np , the NPs also self-assemble into chains, while being tilted with respect to the tubule's axis.more » « less
-
more » « less
Abstract Aluminyl anions are low‐valent, anionic, and carbenoid aluminum species commonly found stabilized with potassium cations from the reaction of Al‐halogen precursors and alkali compounds. These systems are very reactive toward the activation of
σ ‐bonds and in reactions with electrophiles. Various research groups have detected that the potassium atoms play a stabilization role via electrostatic and cationinteractions with nearby (aromatic)‐carbocyclic rings from both the ligand and from the reaction with unsaturated substrates. Since stabilizing K⋯H bonds are witnessed in the activation of this class of molecules, we aim to unveil the role of these metals in the activation of the smaller and less polarizable H2molecule, together with a comprehensive characterization of the reaction mechanism. In this work, the activation of H2utilizing a NON‐xanthene‐Al dimer, [K{Al(NON)}]2( D ) and monomeric, [Al(NON)]−(M ) complexes are studied using density functional theory and high‐level coupled‐cluster theory to reveal the potential role of K+atoms during the activation of this gas. Furthermore, we aim to reveal whetherD is more reactive thanM (or vice versa), or if complicity between the two monomer units exits within theD complex toward the activation of H2. The results suggest that activation energies using the dimeric and monomeric complexes were found to be very close (around 33 kcal mol−1). However, a partition of activation energies unveiled that the nature of the energy barriers for the monomeric and dimeric complexes are inherently different. The former is dominated by a more substantial distortion of the reactants (and increased interaction energies between them). Interestingly, during the oxidative addition, the distortion of the Al complex is minimal, while H2distorts the most, usually over 0.77. Overall, it is found here that electrostatic and induction energies between the complexes and H2are the main stabilizing components up to the respective transition states. The results suggest that the K+atoms act as stabilizers of the dimeric structure, and their cooperative role on the reaction mechanism may be negligible, acting as mere spectators in the activation of H2. Cooperation between the two monomers in D is lacking, and therefore the subsequent activation of H2is wholly disengaged. -
The phosphatidylinositol 4-phosphate 5-kinase (PIP5K) family of lipid-modifying enzymes generate the majority of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ] lipids found at the plasma membrane in eukaryotic cells. PI(4,5)P 2 lipids serve a critical role in regulating receptor activation, ion channel gating, endocytosis, and actin nucleation. Here, we describe how PIP5K activity is regulated by cooperative binding to PI(4,5)P 2 lipids and membrane-mediated dimerization of the kinase domain. In contrast to constitutively dimeric phosphatidylinositol 5-phosphate 4-kinase (PIP4K, type II PIPK), solution PIP5K exists in a weak monomer–dimer equilibrium. PIP5K monomers can associate with PI(4,5)P 2 -containing membranes and dimerize in a protein density-dependent manner. Although dispensable for cooperative PI(4,5)P 2 binding, dimerization enhances the catalytic efficiency of PIP5K through a mechanism consistent with allosteric regulation. Additionally, dimerization amplifies stochastic variation in the kinase reaction velocity and strengthens effects such as the recently described stochastic geometry sensing. Overall, the mechanism of PIP5K membrane binding creates a broad dynamic range of lipid kinase activities that are coupled to the density of PI(4,5)P 2 and membrane-bound kinase.more » « less
-
The phosphatidylinositol 4-phosphate 5-kinase (PIP5K) family of lipid modifying enzymes generate the majority of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) lipids found at the plasma membrane in eukaryotic cells. PI(4,5)P2 lipids serve a critical role in regulating receptor activation, ion channel gating, endocytosis, and actin nucleation. Here we describe how PIP5K activity is regulated by cooperative binding to PI(4,5)P2 lipids and membrane-mediated dimerization of the kinase domain. In contrast to constitutively dimeric phosphatidylinositol 5-phosphate 4-kinase (PIP4K, type II PIPK), solution PIP5K exists in a weak monomer-dimer equilibrium. PIP5K monomers can associate with PI(4,5)P2 containing membranes and dimerize in a protein density dependent manner. Although dispensable for PI(4,5)P2 binding and lipid kinase activity, dimerization enhances the catalytic efficiency of PIP5K through a mechanism consistent with allosteric regulation. Additionally, dimerization amplifies stochastic variation in the kinase reaction velocity and strengthens effects such as the recently described stochastic geometry sensing. Overall, the mechanism of PIP5K membrane binding creates a broad dynamic range of lipid kinase activities that are coupled to the density of PI(4,5)P2 and membrane bound kinase.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d2sm01574a
