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.


Title: Intracellular delivery of virus-like particles using a sheddable linker
To overcome the challenge of lysosomal degradation of material in cells, we developed a carrier using chemical synthesis to successfully bypass the endosomal trap and deliver therapeutic materials directly into the cytoplasm of cells.  more » « less
Award ID(s):
2003534
PAR ID:
10476436
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ; ; ;
Publisher / Repository:
RSC
Date Published:
Journal Name:
Journal of Materials Chemistry B
Volume:
11
Issue:
30
ISSN:
2050-750X
Page Range / eLocation ID:
7126 to 7133
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract Glucocorticoids contribute to the daily migration patterns of T cells in well-nourished organisms and are elevated in the malnourished. We examined the effect of malnutrition on T cell migration by comparing the migration patterns of adoptively transferred malnourished and control T cells in the lymphoid organs of malnourished and control recipients. We found that malnourished T cells generally entered lymphoid tissues more efficiently than control T cells, regardless of recipient. Strikingly, the bone marrow of malnourished recipients attracted naïve malnourished T cells, but not control T cells, more efficiently than control bone marrow. In contrast, the spleens of malnourished and control mice attracted similar numbers of naïve T cells. Further experiments revealed that T cells residing in the bone marrow of malnourished mice express higher levels of CCR7 and lower levels of CD11a than control T cells. We also examined the effect of T cell-specific deficiency of the glucocorticoid receptor on T cell migration to the bone marrow in malnourished mice. Indeed, similarly low percentages of glucocorticoid receptor deficient T cells were observed in the bone marrow of malnourished and control mice, indicating that T cell expression of the glucocorticoid receptor is required for T cell migration to the bone marrow. Overall, we have determined that malnutrition modifies both the bone marrow and naïve T cells to promote naïve T cell migration to the bone marrow and that at least the T cell-specific effects are mediated via the glucocorticoid receptor. NSF-MRI [DBI- 1920116] NSF-RUI [IOS-1951881] 
    more » « less
  2. Abstract Arabidopsis leaf epidermal cells have a wide range of sizes and ploidies, but how large cells are spatially patterned alongside smaller cells remains unclear. Here, we demonstrate that the same genetic pathway that creates giant cells in sepals is also responsible for their formation in the leaf epidermis. In both sepals and leaves, giant cells are scattered among smaller cells; therefore, we asked whether the spatial arrangement of giant cells is random. By comparing sepal and leaf epidermises with computationally generated randomized tissues we show that giant cells are clustered more than is expected by chance. Our cell-autonomous and stochastic computational model recapitulates the observed giant cell clustering, indicating that clustering emerges as a result of the cell division pattern. Overall, cell size patterning is developmentally regulated by common mechanisms in leaves and sepals rather than a simple byproduct of cell growth. TeaserThe spatial pattern of giant cells becomes non-random as the surrounding cells divide. 
    more » « less
  3. Abstract The recurrence of cancer following chemotherapy treatment is a major cause of death across solid and hematologic cancers. In B-cell acute lymphoblastic leukemia (B-ALL), relapse after initial chemotherapy treatment leads to poor patient outcomes. Here we test the hypothesis that chemotherapy-treated versus control B-ALL cells can be characterized based on cellular physical phenotypes. To quantify physical phenotypes of chemotherapy-treated leukemia cells, we use cells derived from B-ALL patients that are treated for 7 days with a standard multidrug chemotherapy regimen of vincristine, dexamethasone, and L-asparaginase (VDL). We conduct physical phenotyping of VDL-treated versus control cells by tracking the sequential deformations of single cells as they flow through a series of micron-scale constrictions in a microfluidic device; we call this method Quantitative Cyclical Deformability Cytometry. Using automated image analysis, we extract time-dependent features of deforming cells including cell size and transit time (TT) with single-cell resolution. Our findings show that VDL-treated B-ALL cells have faster TTs and transit velocity than control cells, indicating that VDL-treated cells are more deformable. We then test how effectively physical phenotypes can predict the presence of VDL-treated cells in mixed populations of VDL-treated and control cells using machine learning approaches. We find that TT measurements across a series of sequential constrictions can enhance the classification accuracy of VDL-treated cells in mixed populations using a variety of classifiers. Our findings suggest the predictive power of cell physical phenotyping as a complementary prognostic tool to detect the presence of cells that survive chemotherapy treatment. Ultimately such complementary physical phenotyping approaches could guide treatment strategies and therapeutic interventions. Insight box Cancer cells that survive chemotherapy treatment are major contributors to patient relapse, but the ability to predict recurrence remains a challenge. Here we investigate the physical properties of leukemia cells that survive treatment with chemotherapy drugs by deforming individual cells through a series of micron-scale constrictions in a microfluidic channel. Our findings reveal that leukemia cells that survive chemotherapy treatment are more deformable than control cells. We further show that machine learning algorithms applied to physical phenotyping data can predict the presence of cells that survive chemotherapy treatment in a mixed population. Such an integrated approach using physical phenotyping and machine learning could be valuable to guide patient treatments. 
    more » « less
  4. Cell signaling through direct physical cell–cell contacts plays vital roles in biology during development, angiogenesis, and immune response. Intercellular communication mechanisms between synthetic cells constructed from the bottom up are majorly reliant on diffusible chemical signals, thus limiting the range of responses in receiver cells. Engineering contact‐dependent signaling between synthetic cells promises to unlock more complicated signaling schemes with spatial responses. Herein, a light‐activated contact‐dependent communication scheme for synthetic cells is designed and demonstrated. A split luminescent protein is utilized to limit signal generation exclusively to contact interfaces of synthetic cells, driving the recruitment of a photoswitchable protein in receiver cells, akin to juxtacrine signaling in living cells. The modular design not only demonstrates contact‐dependent communication between synthetic cells but also provides a platform for engineering orthogonal contact‐dependent signaling mechanisms. 
    more » « less
  5. Abstract During vertebrate retinal development, transient populations of retinal progenitor cells with restricted cell fate choices are formed. One of these progenitor populations expresses the Thrb gene and can be identified by activity of the ThrbCRM1 cis-regulatory element. Short-term assays have concluded that these cells preferentially generate cone photoreceptors and horizontal cells, however developmental timing has precluded an extensive cell type characterization of their progeny. Here we describe the development and validation of a recombinase-based lineage tracing system for the chicken embryo to further characterize the lineage of these cells. The ThrbCRM1 element was found to preferentially form photoreceptors and horizontal cells, as well as a small number of retinal ganglion cells. The photoreceptor cell progeny are exclusively cone photoreceptors and not rod photoreceptors, confirming that ThrbCRM1 progenitor cells are restricted from the rod fate. In addition, specific subtypes of horizontal cells and retinal ganglion cells were overrepresented, suggesting that ThrbCRM1 progenitor cells are not only restricted for cell type, but for cell subtype as well. 
    more » « less