Decrease in pH destabilizes individual vault nanocages by weakening the inter-protein lateral interaction

Llauró, Aida; Guerra, Pablo; Kant, Ravi; Bothner, Brian; Verdaguer, N.; Pablo, Pedro

doi:10.1038/srep34143

Cited by 20 publications

(21 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mechanical studies of protein shells are not limited to viruses containing the native genomic content 136 . For example, experiments have been performed on cowpea chlorotic mottle virus loaded with phthalocyanine dyes 137 , bacterial nanocompartment encapsulins and Aquifex aeolicus lumazine synthase 138,139 , eukaryotic vaults 140 and artificial designer protein shells such as octahedral O3-33 cages 138 . Virus-cell interactions can also be characterized by AFM, and the initial binding of both influenza and rabies viruses to eukaryotic cells has been shown to be multivalent 141,142 .…”

Section: Case Studiesmentioning

confidence: 99%

Atomic force microscopy-based mechanobiology

et al. 2018

View full text Add to dashboard Cite

Mechanobiology focuses on how physical forces and the mechanical properties of proteins, protein assemblies, cells and tissues contribute to signalling, development, cell division, differentiation and sorting, physiology and disease 1-4. On virtually any scale, ranging from organisms 2,4 to components such as organs 5,6 , tissues 3,7 , cells 8-10 , viruses 11,12 , complex extracellular or intracellular architecture (including vesicles, the extracellular matrix or actin network 13,14) or single proteins 15-17 , biological systems respond to mechanical forces and generate mechanical cues. In mechanobiology, living systems are described by cycles of mechanosensation, mechanotransduction and mechanoresponse 2,18. In addition to its state, the functional response of a living system depends on the nature of the mechanical signal, whether it is applied at the nanometre or micrometre scale, for a short or long time, with low or high magnitude, and on whether it is scalar or vectorial. Nanotechnological and microtechnological approaches have enabled tremendous progress in quantifying the mechanical properties of biological systems. The links between mechanical response, morphology and function, however, are conspicuously ill understood. The most widely used approaches to structurally map the mechanical properties and responses of biological systems, ranging from millimetre to sub-nanometre resolution and from micronewton to piconewton sensitivity, are based on atomic force microscopy (AFM) 19,20. In this Review, we survey the exciting developments in AFM-based approaches towards the morphological mapping of a wide variety of mechanical properties and the characterization of the functional response of biological systems under physiologically relevant conditions. We further discuss key challenges and caveats that have to be taken into account to overcome the limitations of AFM-based approaches to more fully describe the mechanical properties of living systems and highlight how complementary techniques can contribute to directly linking the functional responses of complex biological systems to mechanical cues. Characterizing biosystems by AFM The introduction of AFM in 1986 opened the door to imaging and manipulating matter at the atomic, molecular and cellular scales and was central to the nascent nanotechnological revolution 21,22. Of particular importance for the characterization of biological systems, atomic force microscopes can operate in aqueous environments and at physiological temperatures. In an atomic force microscope, a cantilever that is several micrometres long and has a molecularly sharp probe at the end is used to trace the sample topography, detecting

show abstract

Section: Case Studiesmentioning

confidence: 99%

Atomic force microscopy-based mechanobiology

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Although it is well known that they participate in these functions, the mechanism through which it intervenes is not defined. Vault structure is highly conserved among different eukaryotic organisms [20,25,33], which indicates the importance of its functions and the putative biocompatibility that it can present as nano-DDSs [33].…”

Section: Eukaryotic Vaultsmentioning

confidence: 99%

“…Under physiological conditions there is a balance between the closed and open conformations (separate halves) of vaults, allowing the entry of molecules [39]. An acidification of the medium destabilizes the bonds between monomers, with the exception of the strong hydrophobic joints between the head-helix domains, giving rise to a “flower-like” structure [20,40]. Low-pH condition triggers vault conformational change.…”

Section: Eukaryotic Vaultsmentioning

confidence: 99%

“…Most requirements for designing an ideal nano-DDS (stability, specificity, or controlled release of the drug) can be acquired using proteins in its structure since protein domains with these functions have been described [15]. As an advantage, proteins can be easily produced in different biological systems [16] such as bacteria [14,17], insect cells [18,19,20], or mammalian cells [21], among others.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Latest Advances in the Development of Eukaryotic Vaults as Targeted Drug Delivery Systems

et al. 2019

View full text Add to dashboard Cite

The use of smart drug delivery systems (DDSs) is one of the most promising approaches to overcome some of the drawbacks of drug-based therapies, such as improper biodistribution and lack of specific targeting. Some of the most attractive candidates as DDSs are naturally occurring, self-assembling protein nanoparticles, such as viruses, virus-like particles, ferritin cages, bacterial microcompartments, or eukaryotic vaults. Vaults are large ribonucleoprotein nanoparticles present in almost all eukaryotic cells. Expression in different cell factories of recombinant versions of the “major vault protein” (MVP) results in the production of recombinant vaults indistinguishable from native counterparts. Such recombinant vaults can encapsulate virtually any cargo protein, and they can be specifically targeted by engineering the C-terminus of MVP monomer. These properties, together with nanometric size, a lumen large enough to accommodate cargo molecules, biodegradability, biocompatibility and no immunogenicity, has raised the interest in vaults as smart DDSs. In this work we provide an overview of eukaryotic vaults as a new, self-assembling protein-based DDS, focusing in the latest advances in the production and purification of this platform, its application in nanomedicine, and the current preclinical and clinical assays going on based on this nanovehicle.

show abstract

“…Another experiment showed that decreasing the pH weakened the bonds between proteins. It was proposed that the observed responses of the vaults at low pH values were due to the strong polar characteristic of the lateral interaction between adjacent proteins 256 . It also has been shown that the vault maintained its structure at pH values ranging from 6.0 to 7.5, but the particle was reported to be 15% shorter in length at pH 6.0 compared to its length at pH 7.5.…”

Section: - Ncs As Platforms For Ddssmentioning

confidence: 99%

Nanocaged platforms: modification, drug delivery and nanotoxicity. Opening synthetic cages to release the tiger

et al. 2017

View full text Add to dashboard Cite

Nanocages (NCs) have emerged as a new class of drug-carriers, with a wide range of possibilities in multi-modality medical treatments and theranostics. Nanocages can overcome such limitations as high toxicity caused by anti-cancer chemotherapy or by the nanocarrier itself, due to their unique characteristics. These properties consist of: (1) a high loading-capacity (spacious interior); (2) porous structure (analogous to openings between the bars of the cage); (3) enabling smart release (a key to unlock the cage); and (4) a low likelihood of unfavorable immune responses (the outside of the cage is safe). In this review, we cover different classes of NC structures such as virus-like particles (VLPs), protein NCs, DNA NCs, supramolecular nanosystems, hybrid metal-organic NCs, gold NCs, carbon-based NCs and silica NCs. Moreover, NC-assisted drug delivery including modification methods, drug immobilization, active targeting, and stimulus-responsive release mechanisms are discussed, highlighting advantages, disadvantages and challenges. Finally, translation of NCs into clinical applications, and an up-to-date assessment of the nanotoxicology considerations of NCs are presented.

show abstract

Decrease in pH destabilizes individual vault nanocages by weakening the inter-protein lateral interaction

Cited by 20 publications

References 36 publications

Atomic force microscopy-based mechanobiology

Atomic force microscopy-based mechanobiology

Latest Advances in the Development of Eukaryotic Vaults as Targeted Drug Delivery Systems

Nanocaged platforms: modification, drug delivery and nanotoxicity. Opening synthetic cages to release the tiger

Contact Info

Product

Resources

About