Regulated portals of entry into the cell
TL;DR: ‘Endocytosis’ encompasses several diverse mechanisms by which cells internalize macromolecules and particles into transport vesicles derived from the plasma membrane and must be viewed in a broader context than simple vesicular trafficking.
Abstract: The plasma membrane is the interface between cells and their harsh environment. Uptake of nutrients and all communication among cells and between cells and their environment occurs through this interface. 'Endocytosis' encompasses several diverse mechanisms by which cells internalize macromolecules and particles into transport vesicles derived from the plasma membrane. It controls entry into the cell and has a crucial role in development, the immune response, neurotransmission, intercellular communication, signal transduction, and cellular and organismal homeostasis. As the complexity of molecular interactions governing endocytosis are revealed, it has become increasingly clear that it is tightly coordinated and coupled with overall cell physiology and thus, must be viewed in a broader context than simple vesicular trafficking.
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TL;DR: This Review focuses on recent progress important for the rational design of such nanoparticles and discusses the challenges to realizing the potential of nanoparticles.
Abstract: Engineered nanoparticles have the potential to revolutionize the diagnosis and treatment of many diseases; for example, by allowing the targeted delivery of a drug to particular subsets of cells. However, so far, such nanoparticles have not proved capable of surmounting all of the biological barriers required to achieve this goal. Nevertheless, advances in nanoparticle engineering, as well as advances in understanding the importance of nanoparticle characteristics such as size, shape and surface properties for biological interactions, are creating new opportunities for the development of nanoparticles for therapeutic applications. This Review focuses on recent progress important for the rational design of such nanoparticles and discusses the challenges to realizing the potential of nanoparticles.
3,239 citations
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...Particle size is also known to influence the mechanism of cellular internalizatio...
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TL;DR: These findings suggest that HeLa cells readily internalize nonspherical particles with dimensions as large as 3 μm by using several different mechanisms of endocytosis, and it was found that rod-like particles enjoy an appreciable advantage when it comes to internalization rates.
Abstract: The interaction of particles with cells is known to be strongly influenced by particle size, but little is known about the interdependent role that size, shape, and surface chemistry have on cellular internalization and intracellular trafficking. We report on the internalization of specially designed, monodisperse hydrogel particles into HeLa cells as a function of size, shape, and surface charge. We employ a top-down particle fabrication technique called PRINT that is able to generate uniform populations of organic micro- and nanoparticles with complete control of size, shape, and surface chemistry. Evidence of particle internalization was obtained by using conventional biological techniques and transmission electron microscopy. These findings suggest that HeLa cells readily internalize nonspherical particles with dimensions as large as 3 μm by using several different mechanisms of endocytosis. Moreover, it was found that rod-like particles enjoy an appreciable advantage when it comes to internalization rates, reminiscent of the advantage that many rod-like bacteria have for internalization in nonphagocytic cells.
2,617 citations
TL;DR: An understanding of how synthetic and natural chemical moieties on the nanoparticle surface (in addition to nanoparticle shape and size) impact their interaction with lipid bilayers and cells is presented.
Abstract: The interaction of nanomaterials with cells and lipid bilayers is critical in many applications such as phototherapy, imaging, and drug/gene delivery. These applications require a firm control over nanoparticle-cell interactions, which are mainly dictated by surface properties of nanoparticles. This critical Review presents an understanding of how synthetic and natural chemical moieties on the nanoparticle surface (in addition to nanoparticle shape and size) impact their interaction with lipid bilayers and cells. Challenges for undertaking a systematic study to elucidate nanoparticle-cell interactions are also discussed.
2,346 citations
TL;DR: In vivo biodistribution suggested that NPs with slight negative charges and particle size of 150 nm were tended to accumulate in tumor more efficiently, and could serve as a guideline in the rational design of drug nanocarriers with maximized therapeutic efficacy and predictable in vivo properties.
2,069 citations
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...In addition, NPs with larger size (>150 nm) would be mostly excluded from cellular internalization in that the cut-off particle size of NPs being internalized into non-phagocytic cells by nonspecific endocytosis was 150 nm [24]....
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TL;DR: This review describes the current experimental tools to study endocytosis of nanomedicines and provides specific examples from recent literature and the authors' own work on endocyTosis of Nanomedicine.
1,819 citations
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...It is responsible for uptake of essential nutrients like cholesterol carried into cells by low density lipoprotein (LDL) via the LDL receptor, or iron carried by transferrin (Tf) signaling by internalization and degradation of receptors andmaintaining cellular homeostasis, for example, by trafficking ion pumps [9,12]....
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...In this approach pinocytosis is classified as clathrindependent endocytosis (also known as clathrin-mediated endocytosis (CME)) and clathrin-independent endocytosis [9]....
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References
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TL;DR: Macrophages also play an important role in the recognition and clearance of apoptotic cells; a notable feature of this process is the absence of an inflammatory response.
Abstract: Phagocytosis of pathogens by macrophages initiates the innate immune response, which in turn orchestrates the adaptive response. In order to discriminate between infectious agents and self, macrophages have evolved a restricted number of phagocytic receptors, like the mannose receptor, that recognize conserved motifs on pathogens. Pathogens are also phagocytosed by complement receptors after relatively nonspecific opsonization with complement and by Fc receptors after specific opsonization with antibodies. All these receptors induce rearrangements in the actin cytoskeleton that lead to the internalization of the particle. However, important differences in the molecular mechanisms underlying phagocytosis by different receptors are now being appreciated. These include differences in the cytoskeletal elements that mediate ingestion, differences in vacuole maturation, and differences in inflammatory responses. Infectious agents, such as M. tuberculosis, Legionella pneumophila, and Salmonella typhimurium, enter macrophages via heterogeneous pathways and modify vacuolar maturation in a manner that favors their survival. Macrophages also play an important role in the recognition and clearance of apoptotic cells; a notable feature of this process is the absence of an inflammatory response.
2,774 citations
"Regulated portals of entry into the..." refers background in this paper
...Phagocytosis Phagocytosis in mammals is conducted primarily by specialized cells, including macrophages, monocytes and neutrophils, that function to clear large pathogens such as bacteria or yeast, or large debris such as the remnants of dead cells, arterial deposits of fat, and so o...
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TL;DR: Dendritic cells are adept at endocytosis and express relatively low levels of surface MHC class I and II products and costimu-latory molecules, but can take up antigen tive responses critical for resistance to infections and but do not present it efficiently to T cells.
2,268 citations
Journal Article•
TL;DR: The general protein apparatus used by all eukaryotes for intracellular transport, including secretion and endocytosis, and for triggered exocyTosis of hormones and neurotransmitters, is uncovered.
Abstract: Recent advances have uncovered the general protein apparatus used by all eukaryotes for intracellular transport, including secretion and endocytosis, and for triggered exocytosis of hormones and neurotransmitters. Membranes are shaped into vesicles by cytoplasmic coats which then dissociate upon GTP hydrolysis. Both vesicles and their acceptor membranes carry targeting proteins which interact specifically to initiate docking. A general apparatus then assembles at the docking site and fuses the vesicle with its target.
2,174 citations
"Regulated portals of entry into the..." refers background in this paper
...Neither a dynamin-like molecule nor GTP hydrolysis are required for vesicle formation from the ER or Golg...
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TL;DR: Caveolae constitute an entire membrane system with multiple functions essential for the cell and are capable of importing molecules and delivering them to specific locations within the cell, exporting molecules to extracellular space, and compartmentalizing a variety of signaling activities.
Abstract: The cell biology of caveolae is a rapidly growing area of biomedical research. Caveolae are known primarily for their ability to transport molecules across endothelial cells, but modern cellular techniques have dramatically extended our view of caveolae. They form a unique endocytic and exocytic compartment at the surface of most cells and are capable of importing molecules and delivering them to specific locations within the cell, exporting molecules to extracellular space, and compartmentalizing a variety of signaling activities. They are not simply an endocytic device with a peculiar membrane shape but constitute an entire membrane system with multiple functions essential for the cell. Specific diseases attack this system: Pathogens have been identified that use it as a means of gaining entrance to the cell. Trying to understand the full range of functions of caveolae challenges our basic instincts about the cell.
1,987 citations
"Regulated portals of entry into the..." refers background in this paper
...Caveolae are now known to be present on many cells, and to demarcate cholesterol and sphingolipid-rich microdomains of the plasma membrane, in which many diverse signalling molecules and membrane transporters are concentrate...
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TL;DR: In this article, the authors uncovered the general protein apparatus used by all eukaryotes for intracellular transport, including secretion and endocytosis, and for triggered exocytotic of hormones and neurotransmitters.
Abstract: Recent advances have uncovered the general protein apparatus used by all eukaryotes for intracellular transport, including secretion and endocytosis, and for triggered exocytosis of hormones and neurotransmitters. Membranes are shaped into vesicles by cytoplasmic coats which then dissociate upon GTP hydrolysis. Both vesicles and their acceptor membranes carry targeting proteins which interact specifically to initiate docking. A general apparatus then assembles at the docking site and fuses the vesicle with its target.
1,848 citations