RESUMO
Nanoparticles are widely used in various biomedical applications as drug delivery carriers, imaging probes, single-molecule tracking/detection probes, artificial chaperones for inhibiting protein aggregation, and photodynamic therapy materials. One key parameter of these applications is the ability of the nanoparticles to enter into the cell cytoplasm, target different subcellular compartments, and control intracellular processes. This is particularly the case because nanoparticles are designed to interact with subcellular components for the required biomedical performance. However, cells are protected from their surroundings by the cell membrane, which exerts strict control over entry of foreign materials. Thus, nanoparticles need to be designed appropriately so that they can readily cross the cell membrane, target subcellular compartments, and control intracellular processes.In the past few decades there have been great advancements in understanding the principles of cellular uptake of foreign materials. In particular, it has been shown that internalization of foreign materials (small molecules, macromolecules, nanoparticles) is size-dependent: endocytotic uptake of materials requires sizes greater than 10 nm, and materials with sizes of 10-100 nm usually enter into cells by energy-dependent endocytosis via biomembrane-coated vesicles. Direct access to the cytosol is limited to very specific conditions, and endosomal escape of material appears to be the most practical approach for intracellular processing.In this Account, we describe how cellular uptake and intracellular processing of nanoscale materials can be controlled by appropriate design of size and surface chemistry. We first describe the cell membrane structure and principles of cellular uptake of foreign materials followed by their subcellular trafficking. Next, we discuss the designed surface chemistry of a 5-50 nm particle that offers preferential lipid-raft/caveolae-mediated endocytosis over clathrin-mediated endocytosis with minimum endosomal/lysosomal trafficking or energy-independent direct cell membrane translocation (without endocytosis) followed by cytosolic delivery without endosomal/lysosomal trafficking. In particular, we emphasize that the zwitterionic-lipophilic surface property of a nanoparticle offers preferential interaction with the lipid raft region of the cell membrane followed by lipid raft uptake, whereas a lower number of affinity biomolecules (<25) on the nanoparticle surface offers caveolae/lipid-raft uptake, while an arginine/guanidinium-terminated surface along with a size of <10 nm offers direct cell membrane translocation. Finally, we discuss how nanoprobes can be designed by adapting these surface chemistry and size preference principles so that they can readily enter into the cell, label different subcellular compartments, and control intracellular processes such as trafficking kinetics, exocytosis, autophagy, amyloid aggregation, and clearance of toxic amyloid aggregates. The Account ends with a Conclusions and Outlook where we discuss a vision for the development of subcellular targeting nanodrugs and imaging nanoprobes by adapting to these surface chemistry principles.
Assuntos
Membrana Celular/metabolismo , Nanopartículas/metabolismo , Transporte Biológico/fisiologia , Cavéolas/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Microdomínios da Membrana/metabolismo , Nanopartículas/química , Tamanho da Partícula , Pinocitose/fisiologia , Propriedades de SuperfícieRESUMO
Lipid nanotubules (LNTs) are conduits that form on the membranes of cells and organelles, and they are ubiquitous in all forms of life from archaea and bacteria to plants and mammals. The formation, shape and dynamics of these LNTs are critical for cellular functions, supporting the transport of myriad cellular cargoes as well as communication within and between cells, and they are also widely believed to be responsible for exploitation of host cells by pathogens for the spread of infection and diseases. In vitro kinetic control of LNT formation can considerably enhance the scope of utilization of these structures for disease control and therapy. Here we report a new paradigm for spontaneous lipid nanotubulation, capturing the dynamical regimes of growth, stabilization and retraction of the tubes through the binding of synthetic nanoparticles on supported lipid bilayers (SLBs). The tubulation is determined by the spontaneous binding-unbinding of nanoparticles on the LNTs. The presented methodology could be used to rectify malfunctioning cellular tubules or to prevent the pathogenic spread of diseases through inhibition of cell-to-cell nanotubule formation.
Assuntos
Bicamadas Lipídicas , Nanopartículas , Cinética , Bicamadas Lipídicas/química , Nanopartículas/químicaRESUMO
The antimicrobial and cytotoxic effects of zinc oxide nanomaterials are popularly thought to be occurring due to zinc ion leaching, but the exact mechanism of cytotoxicity is controversial and not fully understood. Recent studies have shown that oxygen vacancy defects in the nanoscale zinc oxide can generate reactive oxygen species (ROS) under dark conditions and may induce cytotoxicity. In this work, we show that the cytotoxicity of zinc oxide nanoparticles is directly correlated with oxygen vacancy defects that generate ROS under dark conditions. More specifically, we designed zinc oxide nanoparticles with controlled oxygen vacancy defects by controlled gallium doping and showed that the ROS generation property of zinc oxide nanoparticles under dark conditions is directly correlated with oxygen vacancy defects. Further studies show that superoxide radicals and hydrogen peroxide are the primary ROS that are produced under dark conditions. These colloidal nanoparticles are used for cell labeling and therapy via intracellular ROS generation without any light exposure. The designed nanoparticle can be used for the formulation of advanced antibacterial and antimicrobial materials and other cell therapy applications.
Assuntos
Nanopartículas , Óxido de Zinco , Antibacterianos/farmacologia , Sobrevivência Celular , Nanopartículas/toxicidade , Oxigênio , Espécies Reativas de Oxigênio , SuperóxidosRESUMO
Cells respond to external stress by altering their membrane lipid composition to maintain fluidity, integrity and net charge. However, in interactions with charged nanoparticles (NPs), altering membrane charge could adversely affect its ability to transport ions across the cell membrane. Hence, it is important to understand possible pathways by which cells could alter zwitterionic lipid composition to respond to NPs without compromising membrane integrity and charge. Here, we report in situ synchrotron X-ray reflectivity (XR) measurements to monitor the interaction of cationic NPs in the form of quantum dots, with phase-separated supported lipid bilayers of different compositions containing an anionic lipid and zwitterionic lipids having variable degrees of stiffness. We observe that the extent of NP penetration into the respective membranes, as estimated from XR data analysis, is inversely related to membrane compression moduli, which was tuned by altering the stiffness of the zwitterionic lipid component. For a particular membrane composition with a discernible height difference between ordered and disordered phases, we were able to observe subtle correlations between the extent of charge on the NPs and the specificity to bind to the charged and ordered phase, contrary to that observed earlier for phase-separated model biomembranes containing no charged lipids. Our results provide microscopic insight into the role of membrane rigidity and electrostatics in determining membrane permeation. This can lead to great potential benefits in rational designing of NPs for bioimaging and drug delivery applications as well as in assessing and alleviating cytotoxicity of NPs.
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Designing of nanoparticles (NPs) for biomedical applications or mitigating their cytotoxic effects requires microscopic understanding of their interactions with cell membranes. Such insight is best obtained by studying model biomembranes which, however, need to replicate actual cell membranes, especially their compositional heterogeneity and charge. In this work we have investigated the role of lipid charge density and packing of phase separated Langmuir monolayers in the penetration and phase specificity of charged quantum dot (QD) binding. Using an ordered and anionic charged lipid in combination with uncharged but variable stiffness lipids we demonstrate how the subtle interplay of zwitterionic lipid packing and anionic lipid charge density can affect cationic nanoparticle penetration and phase specific binding. Under identical subphase pH, the membrane with higher anionic charge density displays higher NP penetration. We also observe coalescence of charged lipid rafts floating amidst a more fluidic zwitterionic lipid matrix due to the phase specificity of QD binding. Our results suggest effective strategies which can be used to design NPs for diverse biomedical applications as well as to devise remedial actions against their harmful cytotoxic effects especially against respiratory diseases.
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Nanopartículas , Pontos Quânticos , Fenômenos Biofísicos , Cátions , LipídeosRESUMO
Amyloid protein aggregation is responsible for a variety of neurodegenerative diseases, and antiamyloidogenic small molecules are identified for inhibiting such protein aggregation at extra-/intracellular space. We show that the nanoparticle form of small molecules offers better antiamyloidogenic performance via enhanced bioavailability and multivalent binding with protein. Here, we report hyperbranched polyglycerol dendrimers terminated with antiamyloidogenic small molecules such as gallate, tyrosine, and trehalose and their potential in inhibiting lysozyme/huntingtin protein aggregation under intra-/extracellular space. The synthesized functional dendrimers are â¼5 nm in size having an average molecular weight of â¼2000 Da, and they are highly biocompatible in nature. We found that functional dendrimers are efficient in micromolar doses with respect to molecular forms that are effective at millimolar concentration. It is observed that the trehalose-terminated dendrimer is more effective in inhibiting protein aggregation, whereas the gallate-terminated dendrimer is more effective in disintegrating mature protein fibrils. This approach can be used to design functional dendrimers as potential nanodrugs for the treatment of various neurodegenerative diseases.
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Dendrímeros , Glicerol , Polímeros , Agregados ProteicosRESUMO
Intracellular/extracellular protein aggregation is linked to a variety of neurodegenerative diseases. Current research focuses on identifying antiamyloidogenic small molecules to inhibit such protein aggregation and associated cytotoxicity. We have recently demonstrated that transforming these antiamyloidogenic small molecules into nanoparticle forms can greatly improve their performance, and biocompatible/biodegradable formulation of such nanoparticles is critical for therapeutic applications. Here, we report polylactide (PL)-based biodegradable nanoparticles for improved neuroprotection against polyglutamine (polyQ) aggregation that is responsible for Huntington's disease. PL is terminated with an antiamyloidogenic trehalose molecule or the neurotransmitter dopamine, and the resultant nanoparticle is loaded with the antiamyloidogenic catechin molecule. The self-assembled nanoparticle is â¼200 nm in size and enters into the neuronal cell, inhibits polyQ aggregation, lowers oxidative stress, and enhances cell proliferation against polyQ aggregates. This biodegradable polymer can be used in nanoformulation of other reported antiamyloidogenic molecules for testing various animal models of neurodegenerative diseases.
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Catequina , Nanopartículas , Animais , Catequina/farmacologia , Neuroproteção , Peptídeos , Poliésteres , Trealose/farmacologiaRESUMO
Bioconjugated nanoparticles are commonly used for targeting cellular/subcellular components, and labeling performance is known to depend on multivalency, i.e., the number of attached biomolecule per particle. However, these multivalency effects are largely unexplored. Here, we show that multivalency of nanoparticle-bound riboflavin controls the cellular interaction, cellular entry/exit mechanism, and subcellular trafficking property. We have synthesized riboflavin-functionalized quantum dot (QD) of 15-25 nm hydrodynamic size with average riboflavin multivalencies of 15, 30, and 70 [designated as QD(RF)15, QD(RF)30, and QD(RF)70, respectively] and investigated their uptake mechanism in riboflavin receptor overexpressed KB cells. We found that increased multivalency from 15 to 70 increases the cellular interaction with QD, shifts the cell uptake mechanism from caveolae-clathrin to exclusive clathrin-mediated endocytosis, and enhances lysosomal trafficking. This work demonstrates the importance of multivalency of bioconjugated molecule at the nanoparticle surface toward biolabeling performance and should be optimized for best performance of designed nanobioconjugate.
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Corantes Fluorescentes/química , Imagem Óptica , Pontos Quânticos/química , Riboflavina/química , Animais , Células CHO , Sobrevivência Celular/efeitos dos fármacos , Cricetulus , Corantes Fluorescentes/farmacologia , Humanos , Hidrodinâmica , Células KB , Estrutura Molecular , Tamanho da Partícula , Riboflavina/farmacologia , Propriedades de SuperfícieRESUMO
Chemically and biochemically functionalized colloidal nanoparticles with appropriate surface chemistry are essential for various biomedical applications. Although a variety of approaches are now available in making such functional nanoparticles and nanobioconjugates, the lack of complementary surface chemistry often leads to poor performance with respect to intended biomedical applications. This feature article will focus on our efforts to make colloidal nanobioconjugates with appropriate/complementary surface chemistry for better performance of a designed nanoprobe with respect to cellular and subcellular targeting applications. In particular, we emphasize polyacrylate-based coating chemistry followed by a conjugation strategy for transforming <10 nm inorganic nanoparticle to colloidal nanoprobe of 20-50 nm hydrodynamic size. We show that a colloidal nanoprobe can be chemically designed to control the cell-nanoparticle interaction, cellular endocytosis, and targeting/labeling of subcellular compartments. Further study should be directed to adapt this surface chemistry to different nanoparticles, fine tune the surface chemistry for targeting/imaging on the subcellular/molecular length scale, and develop a delivery nanocarrier for subcellular compartments.
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Resinas Acrílicas/química , Coloides/química , Nanoconjugados/química , Nanopartículas/química , Organelas/metabolismo , Endocitose/efeitos dos fármacos , Células HeLa , Humanos , Tamanho da Partícula , Multimerização Proteica/efeitos dos fármacos , Propriedades de SuperfícieRESUMO
Interaction of functional nanoparticles with cells and model biomembranes has been widely studied to evaluate the effectiveness of the particles as potential drug delivery vehicles and bioimaging labels as well as in understanding nanoparticle cytotoxicity effects. Charged nanoparticles, in particular, with tunable surface charge have been found to be effective in targeting cellular membranes as well as the subcellular matrix. However, a microscopic understanding of the underlying physical principles that govern nanoparticle binding, uptake, or diffusion on cells is lacking. Here, we report the first experimental studies of nanoparticle diffusion on model biomembranes and correlate this to the existence of nanoscale dynamics and structural heterogeneities using super-resolution stimulated emission depletion (STED) microscopy. Using confocal and STED microscopy coupled with fluorescence correlation spectroscopy (FCS), we provide novel insight on why these nanoparticles show enhanced binding on two-component lipid bilayers as compared to single-component membranes and how binding and diffusion is correlated to subdiffraction nanoscale dynamics and structure. The enhanced binding is also dictated, in part, by the presence of structural and dynamic heterogeneity, as revealed by STED-FCS studies, which could potentially be used to understand enhanced nanoparticle binding in raft-like domains in cell membranes. In addition, we also observe a clear correlation between the enhanced nanoparticle diffusion on membranes and the extent of membrane penetration by the nanoparticles. Our results not only have a significant impact on our understanding of nanoparticle binding and uptake as well as diffusion in cell and biomembranes, but have very strong implications for uptake mechanisms and diffusion of other biomolecules, like proteins on cell membranes and their connections to functional membrane nanoscale platform.
Assuntos
Bicamadas Lipídicas/química , Nanopartículas/química , Adsorção , Difusão , Modelos Moleculares , Conformação MolecularRESUMO
Protein aggregation is linked to variety of neurodegenerative disorders and other diseases. Current research involves understanding the mechanism of protein aggregation, inhibiting protein aggregation under intra/extracellular space, lowering toxicity arising due to soluble oligomers, and augmenting the clearance of protein aggregates from the brain. Toward this direction, different types of antiamyloidogenic small molecules, macromolecules, and nanomaterials are identified that can inhibit protein aggregation, and extensive progress has been made for their effective utilization. Here, we summarize our effort in designing a nanoparticle form of antiamyloidogenic molecules with enhanced performance under in vitro and in vivo conditions. We found that the nanoparticle form of antiamyloidogenic molecules can perform up to 100,000-times better than the respective molecular form due to the combined effect of enhanced bioavailability at intra/extracellular space and multivalent binding property with aggregating protein. This work demonstrates that further research should be directed toward designing nanoparticle forms of antiamyloidogenic molecules for their effective performance.
Assuntos
Encéfalo/efeitos dos fármacos , Nanopartículas/química , Doenças Neurodegenerativas/tratamento farmacológico , Agregados Proteicos/efeitos dos fármacos , Agregação Patológica de Proteínas/tratamento farmacológico , Amiloide/antagonistas & inibidores , Encéfalo/metabolismo , Humanos , Nanopartículas/administração & dosagemRESUMO
Bisphenol A is a well-known endocrine disruptor that comes from plastic/epoxy resin-based consumer products, pollutes our environment and is responsible for various human diseases. Thus, its removal from water/food/the environment is becoming a challenging issue. Here we report the visible light photocatalytic degradation of bisphenol A using a gold nanoparticle based composite with reduced graphene oxide. The nanocomposite captures visible light and produces hydroxyl radicals that oxidize bisphenol A into smaller organic fragments such as phenol derivatives and aliphatic aldehydes/ketones. The composition of the nanocomposite has been optimized for most efficient degradation of bisphenol A under visible light and the approach may be extended for the sunlight-based removal of bisphenol A from water/food/the environment.
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Trehalose is a well-known antiamyloidogenic molecule that inhibits protein aggregation under the intracellular/extracellular condition, and recent work shows that the nanoparticle form of trehalose can further enhance this performance. Here we have designed a trehalose-functionalized Au nanoparticle that can inhibit the aggregation of a polyglutamine-containing mutant protein inside the neuronal cell. Designed nanoparticles have a 20-30 nm Au core with about 350 ± 50 trehalose molecules per particle on the surface on average. They enter the cell, inhibit mutant protein aggregation, and enhance the cell survival against toxic protein aggregates. This work extends the application potential of trehalose for the understanding and treatment of different diseases involving protein aggregation.
Assuntos
Trealose/química , Sobrevivência Celular , Citoplasma , Ouro , Espaço Intracelular , Nanopartículas MetálicasRESUMO
Functionalization of nanoparticles with chemical and biochemical is essential for their biomedical and other application. However, most of the high quality nanoparticles are hydrophobic in nature due to surfactant capping and their conversion into water-soluble functional nanoparticle via appropriate coating and conjugation chemistry is extremely critical issue. Here we report amphiphilic poly(amino acid)-based one-pot coating and conjugation approach that can transform hydrophobic nanoparticle into water-soluble nanoparticle functionalized with primary amine, thiol, and biomolecule. We have designed amphiphilic polyaspartimide that can anchor hydrophobic nanoparticle through octadecyl groups, leaving the polar polyethylene glycol and aspartimide groups exposed outwards. The aspartimide group is then reacted with primary amine containing chemical/biomolecule with the formation of water-soluble functional nanoparticle. This approach has been extended to different hydrophobic nanoparticles and biomolecules. The present approach has advantages over existing approaches as coating and functionalization can be performed in one pot and functional nanoparticles have <12 nm hydrodynamic size, high colloidal stability, and biocompartibility. This developed approach can be used to derive biocompatible nanobioconjugates for various biomedical applications.
Assuntos
Nanopartículas Metálicas/química , Peptídeos/química , Polietilenoglicóis/química , Aminas/química , Animais , Antracenos/química , Arginina/análogos & derivados , Arginina/química , Células CHO , Compostos de Cádmio/química , Cricetulus , Ácido Ditionitrobenzoico/química , Compostos Férricos/química , Fluorescamina/química , Nanopartículas Metálicas/toxicidade , Tamanho da Partícula , Fenantrenos/química , Pontos Quânticos/química , Compostos de Selênio/química , Sulfetos/química , Compostos de Zinco/químicaRESUMO
Understanding of nanoparticle-membrane interactions is useful for various applications of nanoparticles like drug delivery and imaging. Here we report on the studies of interaction between hydrophilic charged polymer coated semiconductor quantum dot nanoparticles with model lipid membranes. Atomic force microscopy and X-ray reflectivity measurements suggest that cationic nanoparticles bind and penetrate bilayers of zwitterionic lipids. Penetration and binding depend on the extent of lipid packing and result in the disruption of the lipid bilayer accompanied by enhanced lipid diffusion. On the other hand, anionic nanoparticles show minimal membrane binding although, curiously, their interaction leads to reduction in lipid diffusivity. It is suggested that the enhanced binding of cationic QDs at higher lipid packing can be understood in terms of the effective surface potential of the bilayers which is tunable through membrane lipid packing. Our results bring forth the subtle interplay of membrane lipid packing and electrostatics which determine nanoparticle binding and penetration of model membranes with further implications for real cell membranes.
Assuntos
Compostos de Cádmio/química , Lipídeos de Membrana/química , Membranas Artificiais , Nanopartículas/química , Polímeros/química , Compostos de Selênio/química , Eletricidade Estática , Sulfetos/química , Compostos de Zinco/química , Sítios de Ligação , Modelos Moleculares , Pontos QuânticosRESUMO
Inhibition of amyloid fibrillation and clearance of amyloid fibrils/plaques are essential for the prevention and treatment of various neurodegenerative disorders involving protein aggregation. Herein, we report curcumin-functionalized gold nanoparticles (Au-curcumin) of hydrodynamic diameter 10-25â nm, which serve to inhibit amyloid fibrillation and disintegrate/dissolve amyloid fibrils. In nanoparticle form, curcumin is water-soluble and can efficiently interact with amyloid protein/peptide, offering enhanced performance in inhibiting amyloid fibrillation and dissolving amyloid fibrils. Our results imply that nanoparticle-based artificial molecular chaperones may offer a promising therapeutic approach to combat neurodegenerative disease.
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Amiloide/antagonistas & inibidores , Amiloide/ultraestrutura , Curcumina/farmacologia , Ouro/farmacologia , Nanopartículas/química , Sequência de Aminoácidos , Amiloide/química , Amiloide/metabolismo , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/ultraestrutura , Curcumina/química , Ouro/química , Humanos , Dados de Sequência Molecular , Nanopartículas/ultraestrutura , Solubilidade/efeitos dos fármacosRESUMO
Nanoparticles usually enter cells through energy-dependent endocytosis that involves their cytosolic entry via biomembrane-coated endosomes. In contrast, direct translocation of nanoparticles with straight access to cytosol/subcellular components without any membrane coating is limited to very selective conditions/approaches. Here we show that nanoparticles can switch from energy-dependent endocytosis to energy-independent direct membrane penetration once an amphiphile is electrostatically bound to their surface. Compared to endocytotic uptake, this direct cell translocation is faster and nanoparticles are distributed inside the cytosol without any lysosomal trafficking. We found that this direct cell translocation option is sensitive to the charges of both the nanoparticles and the amphiphile. We propose that an electrostatically bound amphiphile induces temporary opening of the cell membrane, which allows direct cell translocation of nanoparticles. This approach can be adapted for efficient subcellular targeting of nanoparticles and nanoparticle-based drug delivery application, bypassing the endosomal trapping and lysosomal degradation.
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Nanopartículas , Citosol/metabolismo , Nanopartículas/metabolismo , Endocitose , Endossomos/metabolismo , Sistemas de Liberação de MedicamentosRESUMO
Nonendocytic cell uptake of nanomaterials is challenging, which requires specific surface chemistry and smaller particle size. Earlier works have shown that an arginine-terminated nanoparticle of <10-20 nm size shows nonendocytic uptake via direct membrane penetration. However, the roles of surface arginine density and the arginine-arginine distance at the nanoparticle surface in controlling such nonendocytic uptake mechanism is not yet explored. Here we show that a higher arginine density at the nanoparticle surface with an arginine-arginine distance of <3 nm is the most critical aspect for such nonendocytic uptake. We have used quantum dot (QD)-based nanoparticles as a model for fluorescent tracking inside cells and for quantitative estimation of cellular uptake. We found that arginine-terminated nanoparticles of 10 nm size can opt for the energy-dependent endocytosis pathway if the arginine-arginine distance is >3 nm. In contrast, nanoparticles with <3 nm arginine-arginine distance rapidly enter into the cell via the nonendocytic approach, are freely available in the cytosol in large amounts to capture the cellular adenosine triphosphate (ATP), generate oxidative stress, and induce ATP-deficient cellular autophagy. This work shows that arginine-arginine distance at the nanoparticle surface is another fundamental parameter, along with the particle size, for the nonendocytic cell uptake of foreign materials and to control intracellular activity. This approach may be utilized in designing nanoprobes and nanocarriers with more efficient biomedical performances.
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Nanopartículas , Pontos Quânticos , Arginina , Nanopartículas/metabolismo , Autofagia , Trifosfato de Adenosina , Tamanho da Partícula , EndocitoseRESUMO
Cellular membranes are constantly bombarded with biomolecules and nanoscale particles, and cell functionality depends on the fraction of the bound/internalized entities. Understanding the biophysical parameters underlying this complex process is very difficult in live cells. Model membranes provide an ideal platform to obtain insight into the minimal and essential parameters involved in determining cell membrane-nanoparticle (NP) interaction. Here we report spontaneous binding and unbinding of semiconductor NPs, carrying different net charges and interacting with model biomembranes, using in situ neutron reflectivity (NR) and fluorescence microscopy studies. We observe a critical concentration of NPs above which they spontaneously unbind along with lipids from lipid monolayer membranes, leaving behind fewer bound NPs. This critical concentration varies depending on whether the NPs carry a net charge or are neutral, and is also governed by the extent of NP crowding for a fixed NP charge. The observations suggest a subtle interplay between electrostatics, membrane fluidity, and NP crowding effects, which eventually determines the adsorbed concentration for unbinding transition. Our study provides valuable microscopic insight into the parameters that could determine the biophysical process underlying NP uptake and ejection by cells which, in turn, can be utilized for their potential applications in bioimaging and drug delivery.
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Nanopartículas , Eletricidade Estática , Nanopartículas/química , Membrana Celular/metabolismo , Sistemas de Liberação de Medicamentos , Fluidez de MembranaRESUMO
Biomolecular piezoelectric materials are envisioned for advanced biomedical applications for their robust piezoelectricity, biocompatibility, and flexibility. Here, we report the piezoelectric property of amyloid fibrils derived from three distinct proteins: lysozyme, insulin, and amyloid-ß. We found that piezoelectric properties are dependent on the extent of the ß-sheet structure and the extent of fibril anisotropy. We have observed the piezoelectric constant value in the range of 24-42 pm/V for fibrils made of lysozyme/insulin/amyloid-ß, and for the sheet/bundle-like structure of lysozyme aggregates, the value becomes 62 pm/V. These piezoelectric constant values are 4-10 times higher than the native lysozyme/insulin/amyloid proteins. Computational studies show that extension of the ß-sheet structure produces an asymmetric arrangement of charges (in creating dipole moment) and mechanical stress induces an aligned orientation of these dipoles that results in a piezoelectric effect. It is shown that these piezoelectric fibrils can harvest mechanical as well as ultrasound-based energy to produce a voltage of up to 1 V and a current of up to 13 nA. These fibrils are employed for reactive oxygen species (ROS) generation under ultrasound exposure and utilized for ultrasonic degradation of organic pollutants or killing of cancer cells via intracellular ROS generation under ultrasound exposure. Our findings demonstrate that the piezoelectric property of protein fibrils has potential for wireless therapeutic applications and may have physiological roles that are yet to be explored.