skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


Title: Biomaterial–tight junction interaction and potential impacts
The active pharmaceutical ingredients (APIs) have to cross the natural barriers and get into the blood to impart the pharmacological effects. The tight junctions (TJs) between the epithelial cells serve as the major selectively permeable barriers and control the paracellular transport of the majority of hydrophilic drugs, in particular, peptides and proteins. TJs perfectly balance the targeted transport and the exclusion of other unexpected pathogens under the normal conditions. Many biomaterials have shown the capability to open the TJs and improve the oral bioavailability and targeting efficacy of the APIs. Nevertheless, there is limited understanding of the biomaterial–TJ interactions. The opening of the TJs further poses the risk of autoimmune diseases and infections. This review article summarizes the most updated literature and presents insights into the TJ structure, the biomaterial–TJ interaction mechanism, the benefits and drawbacks of TJ disruption, and methods for evaluating such interactions.  more » « less
Award ID(s):
1809229
PAR ID:
10167432
Author(s) / Creator(s):
; ; ; ; ;
Date Published:
Journal Name:
Journal of Materials Chemistry B
Volume:
7
Issue:
41
ISSN:
2050-750X
Page Range / eLocation ID:
6310 to 6320
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; (, Applied Physics Letters)
    Tunnel junctions (TJs) have recently been proposed as a solution for several III-nitride current problems and to enhance new structures. Reported III-nitride TJs grown by metalorganic chemical vapor deposition (MOCVD) resulted in backward diodes with rectifying behavior in forward bias, even with Mg and Si doping in 10 20  cm −3 . This behavior limits applications in several device structures. We report a TJ structure based on p + In 0.15 Ga 0.85 N/n + In 0.05 Ga 0.95 N, where the n-side of the junction is co-doped with Si and Mg and with electron and hole concentrations in the mid-10 19  cm −3 for both the n and p dopants. Co-doping creates deep levels within the bandgap that enhances tunneling under forward biased conditions. The TJ structure was investigated on both GaN substrates and InGaN templates to study the impact of strain on the TJ I–V characteristics. The resulting TJ I–V and resistivities reported indicate the potential for this TJ approach in several device structures based on III-nitrides. We are not aware of any previous MOCVD grown TJs that show Ohmic performance in both forward and reverse biases. 
    more » « less
  2. ; ; ; ; ; ; ; ; (, Optics Express)
    Recently, the use of bottom-TJ geometry in LEDs, which achieves N-polar-like alignment of polarization fields in conventional metal-polar orientations, has enabled enhancements in LED performance due to improved injection efficiency. Here, we elucidate the root causes behind the enhanced injection efficiency by employing mature laser diode structures with optimized heterojunction GaN/In0.17Ga0.83N/GaN TJs and UID GaN spacers to separate the optical mode from the heavily doped absorbing p-cladding regions. In such laser structures, polarization offsets at the electron blocking layer, spacer, and quantum barrier interfaces play discernable roles in carrier transport. By comparing a top-TJ structure to a bottom-TJ structure, and correlating features in the electroluminescence, capacitance-voltage, and current-voltage characteristics to unique signatures of the N- and Ga-polar polarization heterointerfaces in energy band diagram simulations, we identify that improved hole injection at low currents, and improved electron blocking at high currents, leads to higher injection efficiency and higher output power for the bottom-TJ device throughout 5 orders of current density (0.015–1000 A/cm2). Moreover, even with the addition of a UID GaN spacer, differential resistances are state-of-the-art, below 7 × 10−4Ωcm2. These results highlight the virtues of the bottom-TJ geometry for use in high-efficiency laser diodes. 
    more » « less
  3. ; ; ; ; (, Chemical Science)
    The use of hyperosmolar agents (osmotherapy) has been a major treatment for intracranial hypertension, which occurs frequently in brain diseases or trauma. However, side-effects of osmotherapy on the brain, especially on the blood–brain barrier (BBB) are still not fully understood. Hyperosmolar conditions, termed hyperosmolality here, are known to transiently disrupt the tight junctions (TJs) at the endothelium of the BBB resulting in loss of BBB function. Present techniques for evaluation of BBB transport typically reveal aggregated responses from the entirety of BBB transport components, with little or no opportunity to evaluate heterogeneity present in the system. In this study, we utilized potentiometric-scanning ion conductance microscopy (P-SICM) to acquire nanometer-scale conductance maps of Madin–Darby Canine Kidney strain II (MDCKII) cells under hyperosmolality, from which two types of TJs, bicellular tight junctions (bTJs) and tricellular tight junctions (tTJs), can be visualized and differentiated. We discovered that hyperosmolality leads to increased conductance at tTJs without significant alteration in conductance at bTJs. To quantify this effect, an automated computer vision algorithm was designed to extract and calculate conductance components at both tTJs and bTJs. Additionally, lowering Ca 2+ concentration in the bath facilitates tTJ disruption under hyperosmolality. Strengthening tTJ structure by overexpressing immunoglobulin-like domain-containing receptor 1 (ILDR1) protein abrogates the effect of hyperosmolality. We posit that osmotic stress physically disrupts tTJ structure, as evidenced by super-resolution microscopy. Findings from this study not only provide a high-resolution view of TJ structure and function, but also can inform current osmotherapy and drug delivery strategies for brain diseases. 
    more » « less
  4. ; ; ; (, International Journal of Molecular Sciences)
    Claudins are one of the major components of tight junctions (TJs) that polymerize within the cell membrane and form interactions between cells. Some claudins seal the paracellular space, limiting paracellular flux, while others form selectively permeable ion channels that control the paracellular permeability of small ions. Claudin strands are known to be dynamic and reshape within TJs to accommodate large-scale movements and rearrangements of epithelial tissues. Here, we summarize the recent computational and modeling studies on claudin assembly into tetrameric ion channels and their polymerization into μm long strands within the membrane. Computational studies ranging from all-atom molecular dynamics, coarse-grained simulations, and hybrid-resolution simulations elucidate the molecular nature of claudin assembly and function and provide a framework that describes the lateral flexibility of claudin strands. 
    more » « less
  5. ; ; (, International Conference on Program Comprehension)
    Application Programming Interfaces (APIs) often define protocols -- restrictions on the order of client calls to API methods. API protocols are common and difficult to use, which has generated tremendous research effort in alternative specification, implementation, and verification techniques. However, little is understood about the barriers programmers face when using these APIs, and therefore the research effort may be misdirected. To understand these barriers better, we perform a two-part qualitative study. First, we study developer forums to identify problems that developers have with protocols. Second, we perform a think-aloud observational study, in which we systematically observe professional programmers struggle with these same problems to get more detail on the nature of their struggles and how they use available resources. In our observations, programmer time was spent primarily on four types of searches of the protocol state space. These observations suggest protocol-targeted tools, languages, and verification techniques will be most effective if they enable programmers to efficiently perform state search. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email