Reversible Activation of a Cell-Penetrating Peptide in a Membrane Environment

Schach, Denise; Rock, William; Franz, Johannes; Bonn, Mischa; Parekh, Sapun H.; Weidner, Tobias

doi:10.1021/jacs.5b06720

Cited by 56 publications

(71 citation statements)

References 26 publications

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“…Model membranes simplify investigations of specific peptide-membrane interactions by providing a defined environment. Lipid monolayers are a well-established model membrane system [37] that has been widely used to get information about peptide-membrane interactions [38][39][40][41][42]. We employed saturated lipids, for experimental reasons, with different headgroup charges, i.e.…”

Section: Resultsmentioning

confidence: 99%

SAP(E) – A cell-penetrating polyproline helix at lipid interfaces

Franz

Lelle

Peneva

et al. 2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Cell-penetrating peptides (CPPs) are short membrane-permeating amino acid sequences that can be used to deliver cargoes, e.g. drugs, into cells. The mechanism for CPP internalization is still subject of ongoing research. An interesting family of CPPs is the sweet arrow peptides - SAP(E) - which are known to adopt a polyproline II helical secondary structure. SAP(E) peptides stand out among CPPs because they carry a net negative charge while most CPPs are positively charged, the latter being conducive to electrostatic interaction with generally negatively charged membranes. For SAP(E)s, an internalization mechanism has been proposed, based on polypeptide aggregation on the cell surface, followed by an endocytic uptake. However, this process has not yet been observed directly - since peptide-membrane interactions are inherently difficult to monitor on a molecular scale. Here, we use sum frequency generation (SFG) vibrational spectroscopy to investigate molecular interactions of SAP(E) with differently charged model membranes, in both mono- and bi-layer configurations. The data suggest that the initial binding mechanism is accompanied by structural changes of the peptide. Also, the peptide-model membrane interaction depends on the charge of the lipid headgroup with phosphocholine being a favorable binding site. Moreover, while direct penetration has also been observed for some CPPs, the spectroscopy reveals that for SAP(E), its interaction with model membranes remains limited to the headgroup region, and insertion into the hydrophobic core of the lipid layer does not occur.

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Section: Resultsmentioning

confidence: 99%

SAP(E) – A cell-penetrating polyproline helix at lipid interfaces

Franz

Lelle

Peneva

et al. 2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…Often, a change in amide-I peak ratios indicates a reorientation within protein monolayers. 50,51,52 The Chen group has developed methods to determine the orientation of helix and β-sheet structures. 53,54 However, to the best of our knowledge, the SFG response of a β-helix, has never been analyzed or quantified before with SFG.…”

Section: °C 5 °Cmentioning

confidence: 99%

The Ice Nucleating Protein InaZ is Activated by Low Temperature

Roeters¹,

Golbek²,

Bregnhøj³

et al. 2020

Preprint

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Ice-nucleation active (INA) bacteria can promote the growth of ice more effectively than any other known material. Utilizing specialized ice-nucleating proteins (INPros), they obtain nutrients from plants by inducing frost damage and, when airborne in the atmosphere, they drive ice nucleation within clouds and may affect global precipitation patterns. Despite their evident environmental importance, the molecular mechanisms behind INProinduced freezing have remained largely elusive. In the present study, we investigated the folding and the structural basis for interactions between water and the ice-nucleating protein InaZ from the INA bacterium Pseudomonas syringae strain R10.79. Using vibrational sum-frequency generation and two-dimensional infrared spectroscopy, we demonstrate that the ice-active repeats of InaZ adopt a β-helical structure in solution and at water surfaces.In this configuration, hydrogen bonding between INPros and water molecules imposes structural ordering on the adjacent water network. The observed order of water increases as the interface is cooled to temperatures close to the melting point of water. Experimental SFG data combined with spectral calculations and molecular-dynamics simulations shows that the INPro reorients at lower temperatures. We suggest that the reorientation can enhance order-inducing water interactions and, thereby, the effectiveness of ice nucleation by InaZ.

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“…[11,12] To inhibit the influence of protein opsonization and off-target effect, as well as promote the specificity to cancer cells, many inactive-active form conversion strategies, such as uncaging, charge conversion, and conformation change, have been developed to modulate the NP-cell interactions in physiological environments. [13][14][15][16][17][18] In these system, the antifouling surfaces (such as PEGylated surface or zwitterionic surface) act as inactive form to minimize the protein adsorption, reduce the macrophages uptake, and prolong the systemic circulation of the NPs. [19][20][21] The NPs conversion can be achieved by cleaving the antifouling surface by endogenous signals (such as pH and enzymes) or exogenous signals (such as photo), to expose the internal targeting segments for cell recognition.…”

Section: Doi: 101002/adtp201800013mentioning

confidence: 99%

Sequential Antifouling Surface for Efficient Modulation of the Nanoparticle–Cell Interactions in Protein‐Rich Environments

Zhang

Kong

Liu

et al. 2018

Advanced Therapeutics

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Modulating the nanoparticle (NP)-cell interactions in protein-rich environments is of increasing significance to nanomedicine. One major challenge is that the synthetic identity (such as targeting) of NPs endowed for this purpose can be adversely altered by opsonization processes. The formed protein corona on NPs can cause fast clearance of NPs by macrophages and reduced cancer cell uptake. The transformable NPs, which are grafted with a cleavable antifouling surface to achieve inactive-active targeting form conversion, offer great promise to efficiently modulate NP-cell interactions. However, most of the transformable NPs lack a sustainable protection mechanism to avoid the influence of the protein corona during the post-transformation period, leading to the re-opsonization on NPs. Here, the authors design a smart transformable nanosystem with a photo-triggered zwitterion-induced sequential antifouling surface to efficiently reduce protein adsorption on NPs and modulate the NP-cell interactions in protein-rich environments. The authors demonstrate that the primary PEGylated antifouling surface could protect the NPs against uptake by macrophages. Furthermore, the photo-induced secondary zwitterionic antifouling surface is shown to preserve the targeting capacity of biotin-modified NPs during the post-transformation period in protein-rich environments. In contrast, the biotin-conjugated NPs without antifouling surfaces almost lost the targeting specificity in protein-rich environment.

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Reversible Activation of a Cell-Penetrating Peptide in a Membrane Environment

Cited by 56 publications

References 26 publications

SAP(E) – A cell-penetrating polyproline helix at lipid interfaces

SAP(E) – A cell-penetrating polyproline helix at lipid interfaces

The Ice Nucleating Protein InaZ is Activated by Low Temperature

Sequential Antifouling Surface for Efficient Modulation of the Nanoparticle–Cell Interactions in Protein‐Rich Environments

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