How does a virus bud?

Lerner, Daniel M.; Oster, George

doi:10.1016/s0006-3495(93)81071-3

Cited by 27 publications

(36 citation statements)

References 19 publications

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“…Experiments in vitro showed that the uptake kinetics is strongly dependent on the particle size and shape [8][9][10][11]. Analytical models [2,12,13] concerning single NP endocytosis elegantly derived that the endocytic time minimizes at an optimal particle radius of $25 nm, which appears to agree well with experiments. However, the optimal size of the minimal endocytic time may not necessarily correlate to that of the highest uptake rate since the kinetics of simultaneous endocytosis of many NPs might be considerably different from the single-NP models.…”

supporting

confidence: 62%

“…week ending 24 SEPTEMBER 2010 where l k ¼ bk g c. This two-dimensional (in k and l dimensions) wrapping-size distribution function is different from previous models [2,12,13,[15][16][17][18] in that the receptor density in NP-membrane bound regions depends on the degree of wrapping. For convenience, we hereafter denote the double summation appeared in Eq.…”

mentioning

confidence: 74%

“…Inspired by viral invasion of cells [1][2][3], significant efforts have been recently devoted to the design of synthetic nanoparticles (NPs) as drug carriers and/or imaging contrast agents [4][5][6][7]. The NPs are surface coated with ligands (e.g., antibody, peptide, and aptamer) that specifically target surface proteins (receptors) of cancer cells, thereby enhancing therapeutic efficacy and mitigating adverse side effects.…”

mentioning

confidence: 99%

“…Our choice of the physical constants is guided by the existing experimental data or literature whenever possible. Unless otherwise explicitly mentioned, we choose A 0 ¼ 225 nm 2 6 (corresponding to a membrane area of 10 m cell), and ' ¼ 10 À5 . All the values without specified units are in reduced units.…”

mentioning

confidence: 99%

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Variable Nanoparticle-Cell Adhesion Strength Regulates Cellular Uptake

et al. 2010

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confidence: 62%

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confidence: 74%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Variable Nanoparticle-Cell Adhesion Strength Regulates Cellular Uptake

et al. 2010

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“…Simons and Garoff (20,21) suggested that the viral capsid may wrap itself in the host membrane via thermal fluctuations of the membrane. Lerner et al (22) proposed several possible rate-limiting processes to explain virus budding and found that a nonzero spontaneous membrane curvature may be necessary to ensure a wrapping time in accordance with the experimentally observed upper limit of Ϸ20 min. Recently, van Effenterre and Roux (23) and Tzlil et al (24) developed statistical thermodynamics models of virus budding.…”

mentioning

confidence: 57%

Mechanics of receptor-mediated endocytosis

Gao

Shi

Freund

2005

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

1,124

1,067

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Most viruses and bioparticles endocytosed by cells have characteristic sizes in the range of tens to hundreds of nanometers. The process of viruses entering and leaving animal cells is mediated by the binding interaction between ligand molecules on the viral capid and their receptor molecules on the cell membrane. How does the size of a bioparticle affect receptor-mediated endocytosis? Here, we study how a cell membrane containing diffusive mobile receptors wraps around a ligand-coated cylindrical or spherical particle. It is shown that particles in the size range of tens to hundreds of nanometers can enter or exit cells via wrapping even in the absence of clathrin or caveolin coats, and an optimal particles size exists for the smallest wrapping time. This model can also be extended to include the effect of clathrin coat. The results seem to show broad agreement with experimental observations. cell adhesion ͉ vesicle budding ͉ virus ͉ biomembrane ͉ receptor-ligand binding R eceptor-mediated endocytosis is one of the most important processes with which viruses and bioparticles can enter or leave an animal cell. Viruses have thousands of different shapes and sizes. Most viruses show a characteristic size in the range of tens to hundreds of nanometers (1, 2). Equipped with a limited amount of nucleic acid, viruses propagate by parasitizing host cells and multiplying their viral nucleic acid and protein capsid via the biochemical machinery of the host. The life cycle of a virus follows a sequential route through various compartments of the host as illustrated in Fig. 1 (3). It takes only 20-40 min for many bacterial phages to finish one life cycle from infection to lysis. For most animal viruses, entering and leaving a host cell are mediated by specific binding of outer coat proteins (such as hemagglutinin in the case of influenza viruses) to specific mobile receptors on the host cell surface.It has been generally assumed that the endocytosis of viruses is associated with the formation of a clathrin coat at the inner membrane leaflet (4). Typically, clathrin coats can generate a membrane radius of curvature as small as Ϸ50 nm. The formation of such small buds has been explained in terms of the bending elasticity concept by considering topological defects of the clathrin network (5). More recently, however, it has been shown that influenza viruses can enter cells even if the formation of clathrin coats are inhibited (6, 7). Here, we develop a model to explain the mechanism of clathrin-free entry of viruses into cells. This model can easily be extended to account for the effect of a clathrin coat.The endocytic pathway is also of interest for understanding possible mechanisms by which nanomaterials might enter into human or animal cells, a significant issue for the development of gene and drug delivery tools (8, 9), as well as for assessing the potential hazard of nanotechnology on ecology and human health (10)(11)(12)(13)(14).Experimental studies on targeted drug delivery into cells have identified particle size as an...

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Size‐Dependent Endocytosis of Nanoparticles

et al. 2009

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Recent advances in nanotechnology have stimulated novel applications in biomedicine where nanoparticles (NPs) are used to achieve drug delivery and photodynamic therapy. In chemotherapeutic cancer treatment, tumor-specific drug delivery is a topic of considerable research interest for achieving enhanced therapeutic efficacy and for mitigating adverse side effects. Most anticancer agents are incapable of distinguishing between benign and malignant cells, and consequently cause systematic toxicity during cancer treatment. Owing to their small size, ligand-coated NPs can be efficiently directed toward, and subsequently internalized by tumor cells through ligand-receptor recognition and interaction (see Fig. 1), thereby offering an effective approach for specific targeting of tumor cells. For example, branching dendrimers have recently been identified as potential candidates for site-specific drug carriers.[2] NPs have also been exploited in other biomedical applications such as bioimaging [3,4] and biosensing. [5,6] It has been demonstrated that florescent quantum dots are efficient in tumor cell imaging, recognition, and tracking, [3,4] and that gold NPs are capable of detecting small proteins. [5,6] To enable rational design of such NP-based agents, it is essential to understand the underlying mechanisms that govern the transmembrane transport and invagination of NPs in biological cells. In this communication, we present a thermodynamic model for receptormediated endocytosis of ligand-coated NPs. We identify an optimal NP radius at which the cellular uptake reaches a maximum of several thousand at physiologically relevant parameters, and we show that the cellular uptake of NPs is regulated by membrane tension, and can be elaborately controlled by particle size. The optimal NP radius for endocytosis is on the order of 25−30 nm, which is in good agreement with prior estimates. [7] Theoretical models [7−11] have provided insights into the dynamics of receptor-mediated endocytosis based on energetic and kinetic considerations, primarily in the context of virus budding. Lerner et al.[8] argued that the discreteness of membrane wrapping via ligandreceptor binding results in a corrugated energy landscape for NP wrapping, which governs the kinetics of endocytosis. In contrast, Gao et al. [7] proposed that the endocytic rate is limited by

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How does a virus bud?

Cited by 27 publications

References 19 publications

Variable Nanoparticle-Cell Adhesion Strength Regulates Cellular Uptake

Variable Nanoparticle-Cell Adhesion Strength Regulates Cellular Uptake

Mechanics of receptor-mediated endocytosis

Size‐Dependent Endocytosis of Nanoparticles

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