Lipid tail protrusions mediate the insertion of nanoparticles into model cell membranes

Lehn, Reid C. Van; Ricci, Maria Antonietta; Silva, Paulo H.J.; Andreozzi, Patrizia; Reguera, Javier; Voïtchovsky, Kislon; Stellacci, Francesco; Alexander‐Katz, Alfredo

doi:10.1038/ncomms5482

Cited by 193 publications

(253 citation statements)

References 71 publications

(132 reference statements)

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“…Insertion correlates with an increase in nonendocytic cell uptake. 18 Building upon prior studies, 18,20,44−47 the results of this work support a pathway in which amphiphilic NPs insert into lipid bilayers via the iterative, stepwise flipping of charged ligands across the bilayer. Consistent with the experimental results, the PMF calculations (Figure 2) confirm that the flipping free energy barrier and corresponding time scale are significantly lower for NP-grafted charged ligands than for isolated ions, indicating that ligand flipping is possible on physiologically relevant time scales.…”

Section: Discussionsupporting

confidence: 73%

Grafting Charged Species to Membrane-Embedded Scaffolds Dramatically Increases the Rate of Bilayer Flipping

Lehn

Alexander‐Katz

2017

ACS Cent. Sci.

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The cell membrane is a barrier to the passive diffusion of charged molecules due to the chemical properties of the lipid bilayer. Surprisingly, recent experiments have identified processes in which synthetic and biological charged species directly transfer across lipid bilayers on biologically relevant time scales. In particular, amphiphilic nanoparticles have been shown to insert into lipid bilayers, requiring the transport of charged species across the bilayer. The molecular factors facilitating this rapid insertion process remain unknown. In this work, we use atomistic molecular dynamics simulations to calculate the free energy barrier associated with “flipping” charged species across a lipid bilayer for species that are grafted to a membrane-embedded scaffold, such as a membrane-embedded nanoparticle. We find that the free energy barrier for flipping a grafted ligand can be over 7 kcal/mol lower than the barrier for translocating an isolated, equivalent ion, yielding a 5 order of magnitude decrease in the corresponding flipping time scale. Similar results are found for flipping charged species grafted to either nanoparticle or protein scaffolds. These results reveal new mechanistic insight into the flipping of charged macromolecular components that might play an important, yet overlooked, role in signaling and charge transport in biological settings. Furthermore, our results suggest guidelines for the design of synthetic materials capable of rapidly flipping charged moieties across the cell membrane.

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Section: Discussionsupporting

confidence: 73%

Grafting Charged Species to Membrane-Embedded Scaffolds Dramatically Increases the Rate of Bilayer Flipping

Lehn

Alexander‐Katz

2017

ACS Cent. Sci.

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“…MUA-AuNPs were synthesized according to a previously reported protocol with the exception that MUA was used instead of MUS/OT capping ligands36. MUS(s)–AuNPs synthesis followed previously reported methods37 and large particles and aggregates were removed via DGU fractionation.…”

Section: Methodsmentioning

confidence: 99%

A centrifugation-based physicochemical characterization method for the interaction between proteins and nanoparticles

Bekdemir

Stellacci

2016

Nat Commun

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Nanomedicine requires in-depth knowledge of nanoparticle–protein interactions. These interactions are studied with methods limited to large or fluorescently labelled nanoparticles as they rely on scattering or fluorescence-correlation signals. Here, we have developed a method based on analytical ultracentrifugation (AUC) as an absorbance-based, label-free tool to determine dissociation constants (KD), stoichiometry (Nmax), and Hill coefficient (n), for the association of bovine serum albumin (BSA) with gold nanoparticles. Absorption at 520 nm in AUC renders the measurements insensitive to unbound and aggregated proteins. Measurements remain accurate and do not become more challenging for small (sub-10 nm) nanoparticles. In AUC, frictional ratio analysis allows for the qualitative assessment of the shape of the analyte. Data suggests that small-nanoparticles/protein complexes significantly deviate from a spherical shape even at maximum coverage. We believe that this method could become one of the established approaches for the characterization of the interaction of (small) nanoparticles with proteins.

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“…S8. Committor analyses have been used to identify transition states in protein folding, vesicle fusion, and gold nanoparticle insertion (36)(37)(38)(39). A similar analysis can be used in this hybrid active-passive system to analyze the transition between the (i) no attraction and (ii) bound states, and thus identify the threshold of this emergent spinner-spinner interaction.…”

Section: Spinner-spinnermentioning

confidence: 99%

Emergent ultra–long-range interactions between active particles in hybrid active–inactive systems

Steimel

Aragonés

et al. 2016

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

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Particle-particle interactions determine the state of a system. Control over the range of such interactions as well as their magnitude has been an active area of research for decades due to the fundamental challenges it poses in science and technology. Very recently, effective interactions between active particles have gathered much attention as they can lead to out-of-equilibrium cooperative states such as flocking. Inspired by nature, where active living cells coexist with lifeless objects and structures, here we study the effective interactions that appear in systems composed of active and passive mixtures of colloids. Our systems are 2D colloidal monolayers composed primarily of passive (inactive) colloids, and a very small fraction of active (spinning) ferromagnetic colloids. We find an emergent ultra-long-range attractive interaction induced by the activity of the spinning particles and mediated by the elasticity of the passive medium. Interestingly, the appearance of such interaction depends on the spinning protocol and has a minimum actuation timescale below which no attraction is observed. Overall, these results clearly show that, in the presence of elastic components, active particles can interact across very long distances without any chemical modification of the environment. Such a mechanism might potentially be important for some biological systems and can be harnessed for newer developments in synthetic active soft materials.active matter | nonequilibrium | colloids | monolayer | elasticity A ctive-matter systems have received much interest due to their emergent nonequilibrium phase and collective dynamical behavior. This interest is well founded as some of the most ubiquitous and important biological systems or processes can exhibit such emergent nonequilibrium behavior, which is perhaps most recognizable in macroscopic examples ranging from schools of aquatic organisms like rays or fish (1-3), herds of livestock (4), flocks of birds (5-7), and even a mosh pit at a heavy metal concert (8). Active-matter systems are additionally unique in that such phenomena spans multiple length scales from meter to nanometer. At these smaller length scales, it is clear that such dynamical adaptation and phase separation are necessary to perform many vital biological processes. Dense crowds of cells move collectively through tissue during development and in many of the immune response processes, i.e., wound healing (9). Sea urchin sperm cells have been found to phase separate and organize into arrays of vortices when the density of spermatozoa is large enough (10). In fact, a myriad of biological systems, and experimental systems with biological components, have reported swarming (11-13), flocking (6, 14, 15), spiraling (13, 16), and many more nonequilibrium steady states (17,18). It is clear that, in all these systems, a combination of the activity, shape of the active agents, and the environment lead to effective out-ofequilibrium interactions that determine their steady states. These active-matter systems have ...

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Lipid tail protrusions mediate the insertion of nanoparticles into model cell membranes

Cited by 193 publications

References 71 publications

Grafting Charged Species to Membrane-Embedded Scaffolds Dramatically Increases the Rate of Bilayer Flipping

Grafting Charged Species to Membrane-Embedded Scaffolds Dramatically Increases the Rate of Bilayer Flipping

A centrifugation-based physicochemical characterization method for the interaction between proteins and nanoparticles

Emergent ultra–long-range interactions between active particles in hybrid active–inactive systems

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