Search for: All records

As a time-domain analogue of fluorescence imaging, FCS offers valuable insights into molecular dynamics, interactions, and concentrations within living cells. The primary insight generated by FCS is molecular mobility and concentration, which makes it useful for investigating molecular-scale details without the need for enrichment or separation. A specific strength of FCS is the ability to probe protein-protein interactions in live cells and several recent applications in this area are summarized. FCS is also used to investigate plasma membrane protein organization, with many applications to cell surface receptors and the mechanisms of drug binding. Finally, FCS is undergoing continual methodological innovations, such as imaging FCS, SPIM-FCS PIE-FCCS, STED-FCS, three-color FCS, and massively parallel FCS, which extend the capabilities to investigate molecular dynamics at different spatial and temporal scales. These innovations enable detailed examinations of cellular processes, including cellular transport and the spatial organization of membrane proteins. 

Human epidermal growth factor receptors (HER)—also known as EGFR or ErbB receptors—are a subfamily of receptor tyrosine kinases (RTKs) that play crucial roles in cell growth, division, and differentiation. HER4 (ErbB4) is the least studied member of this family, partly because its expression is lower in later stages of development. Recent work has suggested that HER4 can play a role in metastasis by regulating cell migration and invasiveness; however, unlike EGFR and HER2, the precise role that HER4 plays in tumorigenesis is still unresolved. Early work on HER family proteins suggested that there are direct interactions between the four members, but to date, there has been no single study of all four receptors in the same cell line with the same biophysical method. Here, we quantitatively measure the degree of association between HER4 and the other HER family proteins in live cells with a time‐resolved fluorescence technique called pulsed interleaved excitation fluorescence cross‐correlation spectroscopy (PIE‐FCCS). PIE‐FCCS is sensitive to the oligomerization state of membrane proteins in live cells, while simultaneously measuring single‐cell protein expression levels and diffusion coefficients. Our PIE‐FCCS results demonstrate that HER4 interacts directly with all HER family members in the cell plasma membrane. The interaction between HER4 and other HER family members intensified in the presence of a HER4‐specific ligand. Our work suggests that HER4 is a preferred dimerization partner for all HER family proteins, even in the absence of ligands. 

Our ability to produce human-scale biomanufactured organs is limited by inadequate vascularization and perfusion. For arbitrarily complex geometries, designing and printing vasculature capable of adequate perfusion poses a major hurdle. We introduce a model-driven design platform that demonstrates rapid synthetic vascular model generation alongside multifidelity computational fluid dynamics simulations and three-dimensional bioprinting. Key algorithmic advances accelerate vascular generation 230-fold and enable application to arbitrarily complex shapes. We demonstrate that organ-scale vascular network models can be generated and used to computationally vascularize >200 engineered and anatomic models. Synthetic vascular perfusion improves cell viability in fabricated living-tissue constructs. This platform enables the rapid, scalable vascular model generation and fluid physics analysis for biomanufactured tissues that are necessary for future scale-up and production. 

A definitive theory for the optical or electromagnetic force density in condensed matter has remained elusive. Integral in such a theory is how material interfaces are treated. In order to build collective understanding, a general planar interface situation between vacuum and a semi-infinite, non-magnetizable material medium is studied analytically using two electromagnetic force density formulations and an obliquely incident, p-polarized plane wave impinging on the material surface. A form of the Lorentz electromagnetic force density formulation and the Einstein–Laub electromagnetic force density are shown to both predict a total pressure that agrees with that predicted by the so-called “Maxwell–Bartoli” expression modified for oblique incidence. However, the two formulations present different distributions of the total force between the surface and bulk of the material. The quantification of this difference and of the implied outward surface pressure for this broadly applicable field geometry offers opportunities for the experimental determination of a force density theory that accurately predicts experiment. 

A novel wheelchair called PURE ( Personalized Unique Rolling Experience) that uses hands hands-free (HF) torso leanlean-to -steer control has been developed for manual wheelchair users (mWCUs). PURE addresses limitations of current wheelchairs, such as the in ability to use both hands for life experiences instead of propulsion. PURE uses a ball ball-based robot drivetrain to offer a compactcompact, selfself- balancing , omnidirectional mobile device. A custom sensor system convertconverts rider torso motions into direction and speed commands to control PURE, which is especially useful if a rider has minimal torso range of motion. We explored whether PURE’s HF control performed as well as a traditional joystick (JS) human human- robot interface and mWCUsmWCUs, performed as well as able able-bodied users (ABUs). 10 mWCUs and 10 ABUs were trained and tested to drive PURE through courses replicating indoor settingssettings. Each participant adjusted ride sensitivity settings for both HF and JS control . Repeated Repeated-measures MANOVA tests suggested that the number of collisions collisions, completion time time, NASA TLX scores except physical demand , and index of performance performances were similar for HF and JS control and between mWCUs and ABUs for all sections. Th is suggestsuggests that PURE is effective for controlling this new omnidirectional wheelchair by only using torso motion thus leaving both hands to be used for other tasks during propulsion propulsion. 

Despite the impressive performance of recent marine robots, many of their components are non-biodegradable or even toxic and may negatively impact sensitive ecosystems. To overcome these limitations, biologically-sourced hydrogels are a candidate material for marine robotics. Recent advances in embedded 3D printing have expanded the design freedom of hydrogel additive manufacturing. However, 3D printing small-scale hydrogel-based actuators remains challenging. In this study, Free form reversible embedding of suspended hydrogels (FRESH) printing is applied to fabricate small-scale biologically-derived, marine-sourced hydraulic actuators by printing thin-wall structures that are water-tight and pressurizable. Calcium-alginate hydrogels are used, a sustainable biomaterial sourced from brown seaweed. This process allows actuators to have complex shapes and internal cavities that are difficult to achieve with traditional fabrication techniques. Furthermore, it demonstrates that fabricated components are biodegradable, safely edible, and digestible by marine organisms. Finally, a reversible chelation-crosslinking mechanism is implemented to dynamically modify alginate actuators' structural stiffness and morphology. This study expands the possible design space for biodegradable marine robots by improving the manufacturability of complex soft devices using biologically-sourced materials.