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Small (Weinheim An Der Bergstrasse,... Jul 2022Real-time feedback-driven single-particle tracking (RT-FD-SPT) is a class of techniques in the field of single-particle tracking that uses feedback control to keep a... (Review)
Review
Real-time feedback-driven single-particle tracking (RT-FD-SPT) is a class of techniques in the field of single-particle tracking that uses feedback control to keep a particle of interest in a detection volume. These methods provide high spatiotemporal resolution on particle dynamics and allow for concurrent spectroscopic measurements. This review article begins with a survey of existing techniques and of applications where RT-FD-SPT has played an important role. Each of the core components of RT-FD-SPT are systematically discussed in order to develop an understanding of the trade-offs that must be made in algorithm design and to create a clear picture of the important differences, advantages, and drawbacks of existing approaches. These components are feedback tracking and control, ranging from simple proportional-integral-derivative control to advanced nonlinear techniques, estimation to determine particle location from the measured data, including both online and offline algorithms, and techniques for calibrating and characterizing different RT-FD-SPT methods. Then a collection of metrics for RT-FD-SPT is introduced to help guide experimentalists in selecting a method for their particular application and to help reveal where there are gaps in the techniques that represent opportunities for further development. Finally, this review is concluded with a discussion on future perspectives in the field.
Topics: Algorithms; Feedback; Single Molecule Imaging; Spectrum Analysis
PubMed: 35758534
DOI: 10.1002/smll.202107024 -
Small (Weinheim An Der Bergstrasse,... Apr 2020The mechanobiology of receptor-ligand interactions and force-induced enzymatic turnover can be revealed by simultaneous measurements of force response and fluorescence....
The mechanobiology of receptor-ligand interactions and force-induced enzymatic turnover can be revealed by simultaneous measurements of force response and fluorescence. Investigations at physiologically relevant high labeled substrate concentrations require total internal reflection fluorescence microscopy or zero mode waveguides (ZMWs), which are difficult to combine with atomic force microscopy (AFM). A fully automatized workflow is established to manipulate single molecules inside ZMWs autonomously with noninvasive cantilever tip localization. A protein model system comprising a receptor-ligand pair of streptavidin blocked with a biotin-tagged ligand is introduced. The ligand is pulled out of streptavidin by an AFM cantilever leaving the receptor vacant for reoccupation by freely diffusing fluorescently labeled biotin, which can be detected in single-molecule fluorescence concurrently to study rebinding rates. This work illustrates the potential of the seamless fusion of these two powerful single-molecule techniques.
Topics: Biophysics; Biotin; Microscopy, Atomic Force; Microscopy, Fluorescence; Nanotechnology; Streptavidin
PubMed: 32141169
DOI: 10.1002/smll.201906740 -
Small (Weinheim An Der Bergstrasse,... Feb 2022Controlling the time and dose of nanoparticulate drug delivery by administration of small molecule drugs holds promise for efficient and safer therapies. This study...
Controlling the time and dose of nanoparticulate drug delivery by administration of small molecule drugs holds promise for efficient and safer therapies. This study describes a versatile approach of exploiting antibody-ligand interactions for the design of small molecule-responsive nanocarrier and nanocomposite systems. For this purpose, antibody fragments (scFvs) specific for two distinct small molecule ligands are designed. Subsequently, the surface of nanoparticles (liposomes or adeno-associated viral vectors, AAVs) is modified with these ligands, serving as anchor points for scFv binding. By modifying the scFvs with polymer tails, they can act as a non-covalently bound shielding layer, which is recruited to the anchor points on the nanoparticle surface and prevents interactions with cultured mammalian cells. Administration of an excess of the respective ligand triggers competitive displacement of the shielding layer from the nanoparticle surface and restores nanoparticle-cell interactions. The same principle is applied for developing hydrogel depots that can release integrated AAVs or liposomes in response to small molecule ligands. The liberated nanoparticles subsequently deliver their cargoes to cells. In summary, the utilization of different antibody-ligand interactions, different nanoparticles, and different release systems validates the versatility of the design concept described herein.
Topics: Animals; Genetic Vectors; Ligands; Liposomes; Mammals; Nanoparticles; Polymers
PubMed: 34859962
DOI: 10.1002/smll.202105157 -
Small (Weinheim An Der Bergstrasse,... Jan 2020Solid-state nanopores are a single-molecule technique that can provide access to biomolecular information that is otherwise masked by ensemble averaging. A promising...
Solid-state nanopores are a single-molecule technique that can provide access to biomolecular information that is otherwise masked by ensemble averaging. A promising application uses pores and barcoding chemistries to map molecular motifs along single DNA molecules. Despite recent research breakthroughs, however, it remains challenging to overcome molecular noise to fully exploit single-molecule data. Here, an active control technique termed "flossing" that uses a dual nanopore device is presented to trap a proteintagged DNA molecule and up to 100's of back-and-forth electrical scans of the molecule are performed in a few seconds. The protein motifs bound to 48.5 kb λ-DNA are used as detectable features for active triggering of the bidirectional control. Molecular noise is suppressed by averaging the multiscan data to produce averaged intertag distance estimates that are comparable to their known values. Since nanopore feature-mapping applications require DNA linearization when passing through the pore, a key advantage of flossing is that trans-pore linearization is increased to >98% by the second scan, compared to 35% for single nanopore passage of the same set of molecules. In concert with barcoding methods, the dual-pore flossing technique could enable genome mapping and structural variation applications, or mapping loci of epigenetic relevance.
Topics: Biosensing Techniques; DNA; Nanopores
PubMed: 31858745
DOI: 10.1002/smll.201905379 -
Small (Weinheim An Der Bergstrasse,... Mar 2021It is a tough challenge for many decades to decipher the complex relationships between cell behaviors and cellular physical properties. Single particle tracking (SPT)... (Review)
Review
It is a tough challenge for many decades to decipher the complex relationships between cell behaviors and cellular physical properties. Single particle tracking (SPT) with high spatial and temporal resolution has been applied extensively in cell research to understand physicochemical properties of cells and their bio-functions by tracking endogenous or exogenous probes. This review describes the fundamental principles of SPT as well as its applications in intracellular mechanics, membrane dynamics, organelles distribution, and processes of internalization and transport. Finally, challenges and future directions of SPT are also discussed.
Topics: Cell Membrane; Single Molecule Imaging
PubMed: 33533163
DOI: 10.1002/smll.202005133 -
Small (Weinheim An Der Bergstrasse,... Jun 2021The environmental pollution has become a serious issue because the pollutants can cause permanent damage to the DNA, nervous system, and circulating system, resulting in... (Review)
Review
The environmental pollution has become a serious issue because the pollutants can cause permanent damage to the DNA, nervous system, and circulating system, resulting in various incurable diseases, such as organ failure, malformation, angiocardiopathy, and cancer. The effective detection of environmental pollutants is urgently needed to keep them far away from daily life. Among the reported pollutant sensors, luminescent metal-organic frameworks (LMOFs) with tunable structures have attracted remarkable attention to detect the pollutants because of their excellent selectivity, sensitivity, and recyclability. Although lots of metal-organic framework (MOF)-based luminescent sensors have been summarized and discussed in previous reviews, the detection of environmental pollutants, especially radioactive ions and heavy metal ions, still have not been systematically presented. Here, the sensing mechanisms and construction principles of luminescent MOFs are discussed, and the state-of-the-art MOF-based luminescent sensors of environmental pollutants, including pesticides, antibiotics, explosives, VOCs, toxic gas, toxic small molecules, radioactive ions, and heavy metal ions are highlighted. This comprehensive review may further guide the development of luminescent MOFs and promote their practical applications for sensing environmental pollutants.
Topics: Environmental Pollutants; Ions; Luminescence; Metal-Organic Frameworks; Metals, Heavy
PubMed: 33634574
DOI: 10.1002/smll.202005327 -
Small (Weinheim An Der Bergstrasse,... Oct 2021Sonodynamic therapy (SDT) is a novel noninvasive therapeutic modality that combines low-intensity ultrasound and sonosensitizers. Versus photo-mediated therapy, SDT has... (Review)
Review
Sonodynamic therapy (SDT) is a novel noninvasive therapeutic modality that combines low-intensity ultrasound and sonosensitizers. Versus photo-mediated therapy, SDT has the advantages of deeper tissue penetration, high accuracy, and less side effects. Sonosensitizers are critical for therapeutic efficacy during SDT and organic sonosensitizers are important because of their clear structure, easy monitoring, evaluation of drug metabolism, and clinical transformation. Notably, nanotechnology can be used in the field of sonosensitizers and SDT to overcome the inherent obstacles and achieve sustainable innovation. This review introduces organic small molecule sonosensitizers, nano organic sonosensitizers, and their clinical translation by providing ideas and references for the design of sonosensitizers and SDT so as to promote its transformation to clinical applications in the future.
Topics: Combined Modality Therapy; Humans; Nanoparticles; Neoplasms; Ultrasonic Therapy
PubMed: 34350690
DOI: 10.1002/smll.202101976 -
Small (Weinheim An Der Bergstrasse,... Feb 2022Organic phase change materials are used in actuators like wax motors. The solid→liquid phase transition that drives expansion is commonly induced by resistive heating...
Organic phase change materials are used in actuators like wax motors. The solid→liquid phase transition that drives expansion is commonly induced by resistive heating that requires an electrical connection. The use of light to generate a phase change provides a non-contact way to power wax motors. Here, it is demonstrated that small molecules can act as absorbers to enable a photoinduced solid→liquid melting transition in eicosane, a low molecular weight phase change material. Three different small molecule absorbers are utilized: (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO), azobenzene (AZOB), and guaiazulene (GAZ). The GAZ/eicosane mixture is characterized in detail because its absorption extends out to 750 nm, opening up the possibility of using near-infrared diodes as the photon source. The GAZ/eicosane composite is incorporated into a commercial wax motor assembly and 532 nm laser light is used to lift up to 400 g. The temporal response, work and force output, and efficiency are measured, and no loss of lifting capability or degradation is observed after ten cycles of irradiation. The incorporation of small aromatic molecules with low-energy absorption features into phase change materials can provide a general way to make light powered wax motors.
Topics: Phase Transition
PubMed: 34854535
DOI: 10.1002/smll.202105356 -
Small (Weinheim An Der Bergstrasse,... Oct 2019Natural organisms are made of different types of microcompartments, many of which are enclosed by cell membranes. For these organisms to display a proper function, the...
Natural organisms are made of different types of microcompartments, many of which are enclosed by cell membranes. For these organisms to display a proper function, the microcompartments must be selectively permeable. For example, cell membranes are typically permeable toward small, uncharged molecules such as water, selected nutrients, and cell signaling molecules, but impermeable toward many larger biomolecules. Here, it is reported for the first time dynamic compartments, namely surfactant-stabilized double emulsions, that display selective and tunable permeability. Selective permeability is imparted to double emulsions by stabilizing them with catechol-functionalized surfactants that transport molecules across the oil shell of double emulsions only if they electrostatically or hydrophobically attract encapsulants. These double emulsions are employed as semipermeable picoliter-sized vessels to controllably perform complexation reactions inside picoliter-sized aqueous cores. This thus far unmet level of control over the transport of reagents across oil phases opens up new possibilities to use double emulsion drops as dynamic and selectively permeable microcompartments to initiate and maintain chemical and biochemical reactions in picoliter-sized cell-mimetic compartments.
Topics: Anions; Cations; Crystallization; Emulsions; Ferrous Compounds; Fluorescein; Hydrogen-Ion Concentration; Permeability; Solutions; Spectrophotometry, Ultraviolet
PubMed: 31517446
DOI: 10.1002/smll.201903054 -
Small (Weinheim An Der Bergstrasse,... Nov 2019Endohedral metallofullerenes exhibit combined properties from carbon cages as well as internal metal moieties and have great potential in a wide range of applications as... (Review)
Review
Endohedral metallofullerenes exhibit combined properties from carbon cages as well as internal metal moieties and have great potential in a wide range of applications as molecule materials. Along with the breakthrough of mass production of metallofullerenes, their applied research has been greatly developed with more and more new functions and practical applications. For gadolinium metallofullerenes, their water-soluble derivatives have been demonstrated with antitumor activity and unprecedented tumor vascular-targeting therapy. Metallofullerene water-soluble derivatives also can be applied to treat reactive oxygen species (ROS)-induced diseases due to their high antioxidative activity. For magnetic metallofullerenes, the internal electron spin and metal species bring about spin sensitivity, molecular magnets, and spin quantum qubits, which have many promising applications. Metallofullerenes are significant candidates for fabricating useful electronic devices because of their various electronic structures. This Review provides a summary of the metallofullerene studies reported recently, in the fields of tumor inhibition, tumor vascular-targeting therapies, antioxidative activity, spin probes, single-molecule magnets, spin qubits, and electronic devices. This is not an exhaustive summary and there are many other important study results regarding metallofullerenes. All of this research has revealed the irreplaceable role of metallofullerene materials.
Topics: Animals; Electronics; Fullerenes; Humans; Magnetics; Metals; Nanomedicine; Neoplasms
PubMed: 31131986
DOI: 10.1002/smll.201901522