Polyproline‐Polyornithine Diblock Copolymers with Inherent Mitochondria Tropism

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract Mitochondria play critical roles in regulating cell fate, with dysfunction correlating the development of multiple diseases, emphasizing need for engineered nanomedicines that cross biological barriers. Said often target fluctuating mitochondrial properties and/or present inefficient/insufficient cytosolic delivery (resulting poor overall activity), while many require complex synthetic procedures involving targeting residues (hindering clinical translation). The synthesis/characterization polypeptide‐based penetrating diblock copolymers poly‐L‐ornithine (PLO) and polyproline (PLP) (PLO n ‐PLP m , n:m ratio 1:3) are described as mitochondria‐targeting nanocarriers. Synthesis involves a simple two‐step methodology based on N‐carboxyanhydride ring‐opening polymerization, scale‐up optimization using “design experiments” approach. molecular mechanisms behind targetability therapeutic activity investigated through physical/biological processes themselves or moieties poly‐L‐glutamic (PGA)‐based conjugate. Diblock prompt rapid entry via energy‐independent recognize mitochondria mitochondria‐specific phospholipid cardiolipin (CL). Stimuli‐driven conditions polarization dynamics, which decrease efficacy depending disease type/stage, do not compromise copolymer uptake/targetability. exhibit inherent concentration‐dependent anti‐tumorigenic at level. conjugate possesses improved safety, significant penetration, accumulation recognition. These findings may support efficient safe mitochondrial‐targeting nanomedicines.

Language: Английский

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Tutorial: fluorescence lifetime microscopy of membrane mechanosensitive Flipper probes

Nature Protocols, Journal Year: 2024, Volume and Issue: 19(12), P. 3457 - 3469

Published: Aug. 29, 2024

Language: Английский

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Measuring plasma membrane fluidity using confocal microscopy

Nature Protocols, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Language: Английский

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Fluorescence lifetime imaging microscopy of flexible and rigid dyes probes the biophysical properties of synthetic and biological membranes

Biophysical Journal, Journal Year: 2024, Volume and Issue: 123(12), P. 1592 - 1609

Published: May 3, 2024

Sensing of the biophysical properties membranes using molecular reporters has recently regained widespread attention. This was elicited by development new probes exquisite optical and increased performance, combined with developments in fluorescence detection. Here, we report on lifetime imaging various rigid flexible fluorescent dyes to probe synthetic biological at steady state as well upon action external membrane-modifying agents. We tested solvatochromic Nile red 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl) (ammonium salt) (NBD), viscosity sensor Bodipy C

Language: Английский

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VISION — an open-source software for automated multi-dimensional image analysis of cellular biophysics

Journal of Cell Science, Journal Year: 2024, Volume and Issue: 137(20)

Published: Sept. 11, 2024

Environment-sensitive probes are frequently used in spectral and multi-channel microscopy to study alterations cell homeostasis. However, the few open-source packages available for processing of images limited scope. Here, we present VISION, a stand-alone software based on Python analysis with improved applicability. In addition classical intensity-based analysis, our can batch-process multidimensional an advanced single-cell segmentation capability apply user-defined mathematical operations spectra calculate biophysical metabolic parameters single cells. VISION allows 3D temporal mapping properties such as membrane fluidity mitochondrial potential. We demonstrate broad applicability by applying it effect various drugs cellular properties. correlation between potential, protein distribution cell-cell contacts nanodomains cell-derived vesicles. Together code, provide graphical user interface easy adoption.

Language: Английский

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Exploring the sensitivities of experimental techniques to various types of membrane asymmetry using atomistic simulations

Faraday Discussions, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

We use atomistic simulations of lipid bilayers to generate representative datasets from model membranes in vitro , and examine the sensitivity various experimental techniques abundance imbalances compositionally asymmetric bilayers.

Language: Английский

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Elucidating the physicochemical processes of light-activated rotary motors embedded in lipid membranes

Chem, Journal Year: 2025, Volume and Issue: unknown, P. 102574 - 102574

Published: May 1, 2025

Language: Английский

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Sterols in plant biology – Advances in studying membrane dynamics

The Cell Surface, Journal Year: 2025, Volume and Issue: unknown, P. 100147 - 100147

Published: May 1, 2025

Language: Английский

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Actin dynamics sustains spatial gradients of membrane tension in adherent cells

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 16, 2024

Abstract Tension propagates in lipid bilayers over hundreds of microns within milliseconds, precluding the formation tension gradients. Nevertheless, plasma membrane gradients have been evidenced migrating cells and along axons. Here, using a fluorescent probe, we show that exist all adherent cells, whether they migrate or not. Non-adhering do not display We further branched actin increases tension, while membrane-to-cortex attachments facilitate its propagation. is lowest at edge adhesion sites highest protrusions, setting boundaries By providing quantitative mechanistic basis behind organization gradients, our work explains how are actively sustained cells.

Language: Английский

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Materials evaluation using cell-sized liposomes

Analytical Methods, Journal Year: 2024, Volume and Issue: 16(32), P. 5509 - 5518

Published: Jan. 1, 2024

This review introduces various studies on cell-sized liposomes, which facilitate observation for the rapid detection and analysis of diverse materials based their size, dynamic shape changes, phase separation, providing valuable insights.

Language: Английский

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