Receptor-Mediated Endocytosis of Nanoparticles of Various Shapes

Vácha, Robert; Martínez-Veracoechea, Francisco J.; Frenkel, Daan

doi:10.1021/nl2030213

Cited by 454 publications

(525 citation statements)

References 19 publications

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“…Apparently, increased protein density induces percolation, with linear aggregates crossing and forming meshes, which control the radius of the emerging bud. Moreover, unlike previous experimental and theoretical reports, in which the adhesion of spherical and cylindrical particles caused a concave membrane deformation and, therefore, negatively curved vesiculation similar in order of magnitude to the adhered particles (3,5,29,30), we observe budding on the same side of the protein. Our qualitative observations on the budding behavior, as well as our quantitative results (in terms of bud radii), are consistent with in vivo and in vitro experiments of curvatureinducing proteins (9,27,28,31,32).…”

Section: Resultscontrasting

confidence: 99%

“…In all, we find that the anisotropic curvature interactions between the N-BAR protein and the membrane, and the local saddle-like deformations caused by linear aggregation, are prerequisites in inducing positively curved remodeling. Such morphology was observed in experiments with N-BAR-coated vesicles (9), whereas conversely, concave (opposite) vesiculation was reported with isotropically curving particles interacting with the membrane in both experiments and in theory (3,5,29,34). Our observations also are in direct accordance with a theoretical prediction that anisotropic inclusions in membranes undergo attractive interactions, which ultimately drive their linear assembly (7).…”

Section: Resultssupporting

confidence: 89%

“…5A). These vesicular structures already were reported for simple model systems (3,29) and indicate that percolation of the protein at intermediate concentrations may be a decisive factor in positively curved budding. Calculations of membrane bending energy (Supporting Information), inferred from curvature calculations, reveal that the energy linearly depends on a protein (Fig.…”

Section: Resultssupporting

confidence: 68%

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Linear aggregation of proteins on the membrane as a prelude to membrane remodeling

Šimunović

Srivastava

Voth

2013

Proc. Natl. Acad. Sci. U.S.A.

146

185

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Adhesion and insertion of curvature-mediating proteins can induce dramatic structural changes in cell membranes, allowing them to participate in several key cellular tasks. The way proteins interact to generate curvature remains largely unclear, especially at early stages of membrane remodeling. Using a coarse-grained model of Bin/ amphiphysin/Rvs domain with an N-terminal helix (N-BAR) interacting with flat membranes and vesicles, we demonstrate that at low protein surface densities, binding of N-BAR domain proteins to the membrane is followed by a linear aggregation and the formation of meshes on the surface. In this process, the proteins assemble at the base of emerging membrane buds. Our work shows that beyond a more straightforward scaffolding mechanism at high bound densities, the interplay of anisotropic interactions and the local stress imposed by the N-BAR proteins results in deep invaginations and endocytic vesicular bud-like deformations, an order of magnitude larger than the size of the individual protein. Our results imply that by virtue of this mechanism, cell membranes may achieve rapid local increases in protein concentration.coarse-grained simulation | membrane stress | self-assembly | membrane curvature | Gaussian curvature L ipid membranes protect cells and their organelles and serve as mechanical support for proteins involved in signal transduction and cellular trafficking (1). Owing to the way lipids are assembled into bilayers of mesoscopic length and molecular width, membranes behave as elastic and highly dynamic molecular sheets. Their innate multiscale nature is further evident in the local interplay between proteins and lipids, which results in large-scale membrane remodeling characterized by an impressive array of morphologies (2). These properties allow biological membranes to take part in several important cellular processes, as their restructuring is key to enabling communication between cells, formation of organelles, trafficking, division, and cell migration (1).The interactions between individual proteins and lipid molecules alone are insufficient to remodel flat membrane sheets to an appreciable extent, implying that the experimentally observed membrane remodeling is a result of the concerted action of multiple proteins (3) in ways mechanistically differing from the mode of action of a single protein. Considering the multiple timescales required to capture protein dynamics as the membrane deformations are induced, as well as the difficulty in separating individual events of the remodeling process, this mechanism remains largely unclear. It previously was demonstrated that the binding of curvature-inducing nanoparticles may form tubular and vesicular structures, in which particles interact with one another solely via curvature (3-6). Furthermore, analytical theory predicts that anisotropic inclusions may induce budding on the membrane surface (7). However, the way proteins assemble on the membrane and how their oligomerization couples to both local and long-wavelength transformat...

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Section: Resultscontrasting

confidence: 99%

Section: Resultssupporting

confidence: 89%

Section: Resultssupporting

confidence: 68%

See 1 more Smart Citation

Linear aggregation of proteins on the membrane as a prelude to membrane remodeling

Šimunović

Srivastava

Voth

2013

Proc. Natl. Acad. Sci. U.S.A.

146

185

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“…Under another circumstance, one can imagine that as the number of smaller particles in the vesicle increases, the larger particle, due to depletion effects, will be increasingly pushed to the vesicle wall and eventually be spontaneously enveloped by the vesicle. This process resembles that of biomembrane budding during endocytosis but has been largely overlooked in previous studies of biomembrane budding [13][14][15][16].…”

Section: Introductionmentioning

confidence: 98%

Depletion effect and biomembrane budding

et al. 2013

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Depletion effects are well known to lead to phase separation in microsystems consisting of large and small particles with short-range repulsive interactions that act over macromolecular length scales. The equilibrium mechanics between an enveloped colloidal particle and a biomembrane caused by entropy is investigated by using a continuum model. We show that the favorable contact energy stems from entropy, which is sufficient to drive engulfment of the colloidal particle, and deformation of the biomembrane determines the resistance to the engulfment of the colloidal particle. The engulfment process depends on the ratio of the radii of the larger particle and smaller particles and the bending rigidity. The results show insights into the effects of depletion on biomembrane budding and nanoparticle transportation by a vesicle.

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“…Hydrophobic interaction and electrostatic attraction improved the interaction process. Energyindependent endocytosis of NMs with varying shapes and ligand coverage (Figure 4) was simulated by Vácha et al who indicated that endocytosis efficiency was higher for spherocylindrical NMs than for spheres [92]. As for the effect of pH, PAMAM dendrimers can be absorbed onto the negatively charged membrane at a low pH and can even induce hole formation in the membrane when the cor responding protonation levels are employed in the simulation to mimic the different pH conditions (e.g., pH 10, 7 and 5) [93,94].…”

Section: Mathematical and Numerical Modeling Approaches For Nm-biomembrmentioning

confidence: 99%

Advances in The Understanding of Nanomaterial–Biomembrane Interactions and Their Mathematical and Numerical Modeling

Lin

et al. 2013

Nanomedicine

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The widespread application of nanomaterials (NMs), which has accompanied advances in nanotechnology, has increased their chances of entering an organism, for example, via the respiratory system, skin absorption or intravenous injection. Although accumulating experimental evidence has indicated the important role of NM–biomembrane interaction in these processes, the underlying mechanisms remain unclear. Computational techniques, as an alternative to experimental efforts, are effective tools to simulate complicated biological behaviors. Computer simulations can investigate NM–biomembrane interactions at the nanoscale, providing fundamental insights into dynamic processes that are challenging to experimental observation. This paper reviews the current understanding of NM–biomembrane interactions, and existing mathematical and numerical modeling methods. We highlight the advantages and limitations of each method, and also discuss the future perspectives in this field. Better understanding of NM–biomembrane interactions can benefit various fields, including nanomedicine and diagnosis.

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Receptor-Mediated Endocytosis of Nanoparticles of Various Shapes

Cited by 454 publications

References 19 publications

Linear aggregation of proteins on the membrane as a prelude to membrane remodeling

Linear aggregation of proteins on the membrane as a prelude to membrane remodeling

Depletion effect and biomembrane budding

Advances in The Understanding of Nanomaterial–Biomembrane Interactions and Their Mathematical and Numerical Modeling

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