Artificial stimuli-responsive surfaces that can mimic the dynamic function of living systems have attracted much attention. However, there exist few artificial systems capable of responding to dual- or multistimulation as the natural system does. Herein, we synthesize a pH and glucose dual-responsive surface by grafting poly(acrylamidophenylboronic acid) (polyAAPBA) brush from aligned silicon nanowire (SiNW) array. The as-prepared surface can reversibly capture and release targeted cancer cells by precisely controlling pH and glucose concentration, exhibiting dual-responsive AND logic. In the presence of 70 mM glucose, the surface is pH responsive, which can vary from a cell-adhesive state to a cell-repulsive state by changing the pH from 6.8 to 7.8. While keeping the pH at 7.8, the surface becomes glucose responsive--capturing cells in the absence of glucose and releasing cells by adding 70 mM glucose. Through simultaneously changing the pH and glucose concentration from pH 6.8/0 mM glucose to pH 7.8/70 mM glucose, the surface is dual responsive with the capability to switch between cell capture and release for at least 5 cycles. The cell capture and release process on this dual-responsive surface is noninvasive with cell viability higher than 95%. Moreover, topographical interaction between the aligned SiNW array and cell protrusions greatly amplifies the responsiveness and accelerates the response rate of the dual-responsive surface between cell capture and release. The responsive mechanism of the dual-responsive surface is systematically studied using a quartz crystal microbalance, which shows that the competitive binding between polyAAPBA/sialic acid and polyAAPBA/glucose contributes to the dual response. Such dual-responsive surface can significantly impact biomedical and biological applications including cell-based diagnostics, in vivo drug delivery, etc.
Capture and release of cancer cells: a thermoresponsive nanostructured surface is designed to reversibly capture and release cancer cells, wherein hydrophobic interaction helps the realization of target capture/release of cancer cells. The unique nature of the designed platform is based on the synergistic effect of hydrophobic interactions between the smart surface and the hydrophobic anchor (i.e., biotin‐BSA), and topographic interactions between the nanostructured substrates and cancer cells.
Kindlins and talins are integrin-binding proteins that are critically involved in integrin activation, an essential process for many fundamental cellular activities including cell-matrix adhesion, migration, and proliferation. As FERM-domain-containing proteins, talins and kindlins, respectively, bind different regions of β-integrin cytoplasmic tails. However, compared with the extensively studied talin, little is known about how kindlins specifically interact with integrins and synergistically enhance their activation by talins. Here, we determined crystal structures of kindlin2 in the apo-form and the β1-and β3-integrin bound forms. The apo-structure shows an overall architecture distinct from talins. The complex structures reveal a unique integrin recognition mode of kindlins, which combines two binding motifs to provide specificity that is essential for integrin activation and signaling. Strikingly, our structures uncover an unexpected dimer formation of kindlins. Interrupting dimer formation impairs kindlin-mediated integrin activation. Collectively, the structural, biochemical, and cellular results provide mechanistic explanations that account for the effects of kindlins on integrin activation as well as for how kindlin mutations found in patients with Kindler syndrome and leukocyte-adhesion deficiency may impact integrin-mediated processes.I ntegrins, composed of α-and β-subunits, are the major receptors mediating the cell-extracellular matrix (ECM) adhesion (1-3). By connecting specific ECM proteins and diverse cytoskeletal regulators, integrins mediate bidirectional transmembrane signaling (4, 5). Stable integrin-ECM interaction and subsequent signaling require integrin activation, which was reported to be mediated by talin, a 4.1-protein/ezrin/radixin/moesin (FERM) domain-containing protein (6). Recently, kindlins, another family of FERM-containing proteins, were found to play crucial roles in integrin activation and signaling (7-12).The kindlin family consists of three members in vertebrates, kindlin1/2/3, each containing a FERM domain and a PH domain (Fig. 1A) (13). Compared with the typical FERM domain that consists of three lobes (F1, F2, and F3), kindlin-FERM contains an additional N-terminal F0 lobe. In kindlins, the F1 and F2 lobes are split by a largely unstructured insertion and the PH domain, respectively (Fig. 1A). Kindlins, although sharing high sequence similarity (SI Appendix, Fig. S1), show distinct tissue distributions and nonredundant functions. Kindlin1 is expressed mainly in epithelia, and nonfunctional kindlin1 mutations lead to Kindler syndrome, a congenital skin disease (14-16). Expression of kindlin3 is restricted to the hematopoietic system, and mutations in kindlin3 were found to associate with leukocyte-adhesion deficiency type III (LADIII) (17, 18). Kindlin2 is ubiquitously expressed, and loss of kindlin2 in mice leads to peri-implantation lethality (11). Kindlins are also involved in tumorigenesis and metastasis (19). The kindlin-associated diseases are due, at least in part...
A resettable logic system based on spiropyran‐modified gold nanoparticles that is capable of AND, OR, and INHIBIT logic operations has been constructed. Several methods can record the output of this process, including the naked eye, UV/Vis spectroscopy, determination of the ζ potential, and dynamic light scattering. These logic gates can also detect copper(II) ions in aqueous media.
A series of ZIF-derived Fe-N codoped carbon materials with a well-defined morphology, high surface area, tunable sizes and porous nanoframe structure was successfully prepared by synthesizing Fe-doped ZIF-8 through the assembly of Zn ions with 2-methylimidazole in the presence of iron(III) acetylacetonate, followed by pyrolysis at a high temperature and in an Ar atmosphere. The prepared optimum catalyst materials exhibited excellent activity for the oxygen reduction reaction (ORR) and outstanding durability in both acidic and alkaline solutions. We found that Fe doping during the ZIF-8 synthesis stage was crucial to achieve the materials' well-defined morphology, tunable size, good particle dispersion, and high performance. XPS revealed that Fe doping greatly enhanced the fractions of graphitic-N and pyridinic-N and decreased the fraction of oxidized-N. We suggest that the porosity and high surface area of the nanoframe structure originated from the metal-organic frameworks, the high dispersion of Fe in the nanoframe, and the enhanced proportions of active N species, all of which were responsible for the materials' significantly enhanced ORR performance.
This Article introduces a simple method of cell patterning, inspired by the mussel anchoring protein. Polydopamine (PDA), artificial polymers made from self-polymerization of dopamine (a molecule that resembles mussel-adhesive proteins), has recently been studied for its ability to make modifications on surfaces in aqueous solutions. We explored the interfacial interaction between PDA and poly(ethylene glycol) (PEG) using microcontact printing (μCP). We patterned PDA on several substrates such as glass, polystyrene, and poly(dimethylsiloxane) and realized spatially defined anchoring of mammalian cells as well as bacteria. We applied our system in investigating the relationship between areas of mammalian nuclei and that of the cells. The combination of PDA and PEG enables us to make cell patterns on common laboratorial materials in a mild and convenient fashion.
This paper describes a modular approach to constructing microfluidic systems for the generation of gradients of arbitrary profiles. Unlike most current microfluidic-based systems that have integrated architectures, we design several basic component modules such as distributors, combiners, resistors and collectors and connect them into networks that produce gradients of any profile at will. Using the system as a platform we can generate arbitrary gradient profiles that are tunable in real time. The key advantage of this system is that its operation is based on prefabricated components that are relatively simple. Particularly for non-specialists, the modular microfluidic system is easier to implement and more versatile compared to single, integrated gradient generators. The disadvantages associated with this system is that the total amount of liquids used is rather large compared with single chip-based systems. The system would be useful in simulating environments in vivo, e.g., studying how cells respond to temporal and spatial stimuli.
We report a one-step, mild method to modify antifouling oligo(ethylene glycol)-terminated self-assembled monolayers. We demonstrate for the first time that self-polymerized dopamine, previously reported as an underwater adhesive, can be patterned on typical antifouling surfaces by microfluidic patterning or microcontact printing. The patterns can be applied in spatiotemporal cell patterning.
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