Protein Encapsulation in Mesoporous Silicate:  The Effects of Confinement on Protein Stability, Hydration, and Volumetric Properties

Ravindra, Revanur; Zhao, Shuang; Gies, Hermann; Winter, Roland

doi:10.1021/ja046900n

Cited by 183 publications

(159 citation statements)

References 12 publications

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“…For example, Ravindra et al [32] found that, upon being confined within the pores, with sizes averaging ~25 Å, of a silica glass, the melting temperature of ribonuclease A is raised by ~30° C. The measured increase in melting temperature for the 124-residue protein is in quantitative agreement with predicted stabilization by pores of such sizes (see Fig. 2).…”

Section: Experimental Studies In the Test Tube Enhancement Of Foldingsupporting

confidence: 65%

“…Two kinds of encapsulation are now widely used. The first is formed by nanoporous silica gels or glasses [32][33][34][35] or polyacrylamide gels [36]; the second is formed by sodium bis(2-ethylhexyl) sulfosuccinate (AOT) reverse micelles [37][38][39][40][41]. In both cases, the cage sizes can be controlled.…”

Section: Experimental Studies In the Test Tube Enhancement Of Foldingmentioning

confidence: 99%

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Protein folding in confined and crowded environments

Zhou

2008

Archives of Biochemistry and Biophysics

152

137

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Confinement and crowding are two major factors that can potentially impact protein folding in cellular environments. Theories based on considerations of excluded volumes predict disparate effects on protein folding stability for confinement and crowding: confinement can stabilize proteins by over 10k B T but crowding has a very modest effect on stability. On the other hand, confinement and crowding are both predicted to favor conformations of the unfolded state which are compact, and consequently may increase the folding rate. These predictions are largely borne out by experimental studies of protein folding under confined and crowded conditions in the test tube. Protein folding in cellular environments is further complicated by interactions with surrounding surfaces and other factors. Concerted theoretical modeling and test-tube and in vivo experiments promise to elucidate the complexity of protein folding in cellular environments.The complexity of the cellular environments in which proteins function is increasingly been appreciated [1]. Potential impacts of two related, but distinct factors, confinement and macromolecular crowding, on protein folding are receiving extensive attention [2][3][4][5]. Confinement arises from encapsulation of proteins in compartments with dimensions on the scales of 10's to 100's Å, which are only moderately larger than the sizes of the proteins themselves. Examples of such compartments include the Anfinsen cage of chaperonins and the exit tunnel of ribosomes. Crowding refers to the exclusion of volumes to proteins of interest by the presence of other macromolecules. The aims of this paper are to discuss potential impacts of confinement and crowding on protein folding and to review the progress made by recent studies on protein folding in confined and crowded conditions and in cellular environments.

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Section: Experimental Studies In the Test Tube Enhancement Of Foldingsupporting

confidence: 65%

Section: Experimental Studies In the Test Tube Enhancement Of Foldingmentioning

confidence: 99%

Protein folding in confined and crowded environments

Zhou

2008

Archives of Biochemistry and Biophysics

152

137

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“…34−36 On the way to the native state, Trp-cage visits a proline-detached (P d ) state lacking a fully formed 3 10 helix, such that Pro12 is detached from the hydrophobic core. 35 Both the I (B 3 ) and P d (B 4 ) states can be identified here in Figure 3, although our states have slightly less helical content than those identified previously.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…The folded medoids (5 1 and 5 2 ) have a cosine value of ∼-0.4 because the Trp residue is packed within the hydrophobic core of the protein. In medoid 5 10 , the Trp side chain actually forms a 90°angle with the wall.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Confinement-Induced States in the Folding Landscape of the Trp-cage Miniprotein

Marino

Bolhuis

2012

J. Phys. Chem. B

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Although protein folding is typically studied in dilute solution, folding in a cell will be affected by interactions with other biomolecules and excluded volume effects. Here, we examine the effect of hydrophobic confinement on folding of the Trp-cage miniprotein. We used replica exchange molecular dynamics simulations to probe the differences between folding in the bulk, on a hydrophobic surface, and confined between two hydrophobic walls. In addition to promotion of helix formation due to reduced conformational entropy of the unfolded state upon confinement, adsorption of Trp-cage to a hydrophobic surface stabilizes intermediate structures not present in the bulk. These new intermediate structures may alter the folding mechanism and kinetics and show the importance of including environmental effects when studying protein folding.

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“…10 nm diameter) 52 can be encapsulated into the mesopore network despite the fact that the pore size is similar to that of protein. 73 Interestingly, Hb (pI = 6.8) is still negatively charged when dissolved in phosphate buffer at pH 7.4. Still, the EE% of Hb reached 97%, while for AP-MSNs the EE% was 43% and for AEP-MSNs, 47%.…”

Section: Protein Loading Studiesmentioning

confidence: 99%

Mesoporous Silica Nanoparticles with Large Pores for the Encapsulation and Release of Proteins

Tu¹,

Boyle²,

Friedrich

et al. 2016

ACS Appl. Mater. Interfaces

120

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Mesoporous silica nanoparticles (MSNs) have been explored extensively as solid supports for proteins in biological and medical applications. Small (< 200 nm) MSNs with ordered large pores (> 5 nm), capable of encapsulating therapeutic small molecules suitable for delivery applications in vivo, are rare however. Here we present small, elongated, cuboidal, MSNs with average dimensions of 90 × 43 nm that possess disk-shaped cavities, stacked on top of each other, which run parallel to the short axis of the particle. Amine-functionalization was achieved by modifying the MSN surface with 3-aminopropyltriethoxysilane or 3-[2-(2-aminoethylamino)ethylamino] propyltrimethoxysilane (AP-MSNs and AEP-MSNs) and were shown to have similar dimensions to the non-functionalized MSNs. The dimensions of these particles, and their large surface areas as measured by nitrogen adsorption-desorption isotherms, make them ideal scaffolds for protein encapsulation and delivery. We therefore investigated the encapsulation and release behavior for seven model proteins (α-lactalbumin, ovalbumin, bovine serum albumin, catalase, hemoglobin, lysozyme and cytochrome c). It was discovered that all types of MSNs used in this study allow rapid encapsulation, with a high loading capacity, for all proteins studied. Furthermore, the release profiles of the proteins were tunable. The variation in both rate and amount of protein uptake and release was found to be determined by the surface chemistry of the MSNs, together with the isoelectric point (pI), and molecular weight of the proteins, as well as by the ionic strength of the buffer. These MSNs with their large surface area and optimal dimensions, provide a scaffold with a high encapsulation efficiency and controllable release profiles for a variety of proteins, enabling potential applications in fields such as drug delivery and protein therapy.

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Protein Encapsulation in Mesoporous Silicate: The Effects of Confinement on Protein Stability, Hydration, and Volumetric Properties

Cited by 183 publications

References 12 publications

Protein folding in confined and crowded environments

Protein folding in confined and crowded environments

Confinement-Induced States in the Folding Landscape of the Trp-cage Miniprotein

Mesoporous Silica Nanoparticles with Large Pores for the Encapsulation and Release of Proteins

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