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Åberg, Christoffer
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Åberg, Christoffer
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Åberg, Christoffer
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Now showing 1 - 10 of 13
- PublicationMapping protein binding sites on the biomolecular corona of nanoparticles(Springer Nature, 2015-03-30)
; ; ; ; ; ; ; Nanoparticles in a biological milieu are known to form a sufficiently long-lived and well-organized 'corona' of biomolecules to confer a biological identity to the particle. Because this nanoparticle-biomolecule complex interacts with cells and biological barriers, potentially engaging with different biological pathways, it is important to clarify the presentation of functional biomolecular motifs at its interface. Here, we demonstrate that by using antibody-labelled gold nanoparticles, differential centrifugal sedimentation and various imaging techniques it is possible to identify the spatial location of proteins, their functional motifs and their binding sites. We show that for transferrin-coated polystyrene nanoparticles only a minority of adsorbed proteins exhibit functional motifs and the spatial organization appears random, which is consistent, overall, with a stochastic and irreversible adsorption process. Our methods are applicable to a wide array of nanoparticles and can offer a microscopic molecular description of the biological identity of nanoparticles.532Scopus© Citations 298 - PublicationNanoparticle accumulation and transcytosis in brain endothelial cell layers(Royal Society of Chemistry, 2013-09)
; ; ; ; ; ; The blood–brain barrier (BBB) is a selective barrier, which controls and limits access to the central nervous system (CNS). The selectivity of the BBB relies on specialized characteristics of the endothelial cells that line the microvasculature, including the expression of intercellular tight junctions, which limit paracellular permeability. Several reports suggest that nanoparticles have a unique capacity to cross the BBB. However, direct evidence of nanoparticle transcytosis is difficult to obtain, and we found that typical transport studies present several limitations when applied to nanoparticles. In order to investigate the capacity of nanoparticles to access and transport across the BBB, several different nanomaterials, including silica, titania and albumin- or transferrin-conjugated gold nanoparticles of different sizes, were exposed to a human in vitro BBB model of endothelial hCMEC/D3 cells. Extensive transmission electron microscopy imaging was applied in order to describe nanoparticle endocytosis and typical intracellular localisation, as well as to look for evidence of eventual transcytosis. Our results show that all of the nanoparticles were internalised, to different extents, by the BBB model and accumulated along the endo–lysosomal pathway. Rare events suggestive of nanoparticle transcytosis were also observed for several of the tested materials.939Scopus© Citations 104 - PublicationBiomolecular coronas provide the biological identity of nanosized materials(Nature Publishing Group, 2012-12-05)
; ; ; The search for understanding the interactions of nanosized materials with living organisms is leading to the rapid development of key applications, including improved drug delivery by targeting nanoparticles, and resolution of the potential threat of nanotechnological devices to organisms and the environment. Unless they are specifically designed to avoid it, nanoparticles in contact with biological fluids are rapidly covered by a selected group of biomolecules to form a corona that interacts with biological systems. Here we review the basic concept of the nanoparticle corona and its structure and composition, and highlight how the properties of the corona may be linked to its biological impacts. We conclude with a critical assessment of the key problems that need to be resolved in the near future.3430Scopus© Citations 2152 - PublicationExperimental and theoretical approach to comparative nanoparticle and small molecule intracellular import, trafficking, and export(Elsevier, 2011-12)
; ; ; ; ; ; Central to understanding how nanoscale objects interact with living matter is the need for reproducible and verifiable data that can be interpreted with confidence. Likely this will be the basis of durable advances in nanomedicine and nanomedical safety. To develop these fields, there is also considerable interest in advancing the first generation of theoretical models of nanoparticle (NP) uptake into cells, and NP biodistribution in general. Here we present an uptake study comparing the outcomes for free molecular dye and NPs labeled with the same dye. A simple flux-based approach is presented to model NP uptake. We find that the intracellular NP concentration grows linearly in time, and that the uptake is essentially irreversible, with the particles accumulating in lysosomes. A wide range of practical challenges, from labile dye release to NP aggregation and the need to account for cell division, are addressed to ensure that these studies yield meaningful kinetic information.1545Scopus© Citations 270 - PublicationTheoretical framework for nanoparticle uptake and accumulation kinetics in dividing cell populationsNano-sized objects interact with biological systems in fundamentally novel ways, thereby holding great promise for targeted drug delivery. It has also been suggested they could constitute a hitherto unseen hazard. Numerous experimental studies in the field are taking place. We consider that the nature of the interactions allows a more fundamental theoretical framework to be developed. In particular, we describe the intimate link that develops between nanoparticle uptake and cell population evolution. Explicit analytical results are given and the theory compared to experimental observations.
523Scopus© Citations 28 - PublicationEffects of the Presence or Absence of a Protein Corona on Silica Nanoparticle Uptake and Impact on Cells(ACS Publications, 2012-06-21)
; ; ; ; ; Nanoparticles enter cells through active processes, thanks to their capability of interacting with the cellular machinery. The protein layer (corona) that forms on their surface once nanoparticles are in contact with biological fluids, such as the cell serum, mediates the interactions with cells in situ. As a consequence of this, here we show that the same nanomaterial can lead to very different biological outcomes, when exposed to cells in the presence or absence of a preformed corona. In particular, silica nanoparticles exposed to cells in the absence of serum have a stronger adhesion to the cell membrane and higher internalization efficiency, in comparison to what is observed in medium containing serum, when a preformed corona is present on their surface. The different exposure conditions not only affect the uptake levels but also result in differences in the intracellular nanoparticle location and impact on cells. Interestingly, we also show that after only one hour of exposure, a corona of very different nature forms on the nanoparticles exposed to cells in the absence of serum. Evidence suggests that these different outcomes can all be connected to the different adhesion and surface properties in the two conditions.2691Scopus© Citations 882 - PublicationNanoparticle Adhesion to the Cell Membrane and Its effect on Nanoparticle Uptake Efficiency(American Chemical Society, 2013-01-09)
; ; ; ; ; The interactions between nanosized particles and living systems are commonly mediated by what adsorbs to the nanoparticle in the biological environment, its biomolecular corona, rather than the pristine surface. Here, we characterize the adhesion toward the cell membrane of nanoparticles of different material and size and study how this is modulated by the presence or absence of a corona on the nanoparticle surface. The results are corroborated with adsorption to simple model supported lipid bilayers using a quartz crystal microbalance. We conclude that the adsorption of proteins on the nanoparticle surface strongly reduces nanoparticle adhesion in comparison to what is observed for the bare material. Nanoparticle uptake is described as a two-step process, where the nanoparticles initially adhere to the cell membrane and subsequently are internalized by the cells via energy-dependent pathways. The lowered adhesion in the presence of proteins thereby causes a concomitant decrease in nanoparticle uptake efficiency. The presence of a biomolecular corona may confer specific interactions between the nanoparticle-corona complex and the cell surface including triggering of regulated cell uptake. An important effect of the corona is, however, a reduction in the purely unspecific interactions between the bare material and the cell membrane, which in itself disregarding specific interactions, causes a decrease in cellular uptake. We suggest that future nanoparticle-cell studies include, together with characterization of size, charge, and dispersion stability, an evaluation of the adhesion properties of the material to relevant membranes.2111Scopus© Citations 650 - PublicationTransferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface(Nature Publishing Group, 2013-01-20)
; ; ; ; ; ; ; ; ; Nanoparticles have been proposed as carriers for drugs, genes and therapies to treat various diseases1, 2. Many strategies have been developed to target nanomaterials to specific or over-expressed receptors in diseased cells, and these typically involve functionalizing the surface of nanoparticles with proteins, antibodies or other biomolecules. Here, we show that the targeting ability of such functionalized nanoparticles may disappear when they are placed in a biological environment. Using transferrin-conjugated nanoparticles, we found that proteins in the media can shield transferrin from binding to both its targeted receptors on cells and soluble transferrin receptors. Although nanoparticles continue to enter cells, the targeting specificity of transferrin is lost. Our results suggest that when nanoparticles are placed in a complex biological environment, interaction with other proteins in the medium and the formation of a protein corona3, 4 can ‘screen’ the targeting molecules on the surface of nanoparticles and cause loss of specificity in targeting.3049Scopus© Citations 1472 - PublicationRole of cell cycle on the cellular uptake and dilution of nanoparticles in a cell population(Nature Publishing Group, 2012-01)
; ; ; Nanoparticles are considered a primary vehicle for targeted therapies because they can pass biological barriers, enter and distribute in cells by energy-dependent pathways1-3. Until now, most studies have shown that nanoparticle properties, such as size4-6 and surface7,8, can affect how cells internalise nanoparticles. Here we show that the different phases of cell growth, which constitute the cell cycle, can also influence nanoparticle uptake. Although cells in different cell cycle phases internalised nanoparticles with similar rates, after 24 hours of uptake the concentration of nanoparticles in the cells is ranked according to the different cell cycle phases: G2/M > S > G0/G1. Nanoparticles were not exported from cells but the internalised nanoparticle concentration is split when the cell divides. Our results suggest that future studies on nanoparticle uptake should consider the cell cycle because in a cell population, the internalised nanoparticle dose in each cell varies as the cell cycles.5875Scopus© Citations 508 - PublicationLipid phase behaviour under steady state conditionsAt the interface between two regions, for example the air–liquid interface of a lipid solution, there can arise non-equilibrium situations. The water chemical potential corresponding to the ambient RH will, in general, not match the water chemical potential of the solution, and the gradients in chemical potential cause diffusional flows. If the bulk water chemical potential is close to a phase transition, there is the possibility of forming an interfacial phase with structures qualitatively different from those found in the bulk. Based on a previous analysis of this phenomenon in two component systems (C. Åberg, E. Sparr, K. J. Edler and H. Wennerström, Langmuir, 2009, 25, 12177), we here analyse the phenomenon for three-component systems. The relevant transport equations are derived, and explicit results are given for some limiting cases. Then the formalism is applied conceptually to four different aqueous lipid systems, which in addition to water and a phospholipid contain (i) octyl glucoside, (ii) urea, (iii) heavy water, and (iv) sodium cholate as the third component. These four cases are chosen to illustrate (i) a method to use a micelle former to transport lipid to the interface where a multi-lamellar structure can form; (ii) to use a co-solvent to inhibit the formation of a gel phase at the interface; (iii) a method to form pure phospholipid multi-lamellar structures at the interface; (iv) a method to form a sequence of phases in the interfacial region. These four cases all have the character of theoretically based conjectures and it remains to investigate experimentally whether or not the conditions can be realized in practice.
431Scopus© Citations 8