Biology subjects

McDonnell, P.

Publications and source records attributed to McDonnell, P..

4 recordsLinked to original sources

bioRxiv2025

Physically intelligent soft antennae enhance tactile perception by active touch

Soft robotic sensors today struggle to interpret complex tactile scenes without incurring significant computational costs. Inspired by insect antennae--compliant, distributed sensors that efficiently process tactile information through physical intelligence--we investigated whether mechanical design and active touch sensing strategies could enhance robotic tactile feature perception. We hypothesized that insect-inspired antenna dynamics, specifically flexural stiffness gradients and active touch speed, could simplify tactile classification. Using a sim-to-real framework that bridges bioinspired computational models with a multi-link soft robot antenna, we introduce the notion of tactile fields--spatiotemporal representations of tactile stimuli shaped by contact location, feature type, and active touch speed. Our analyses show that cockroach-inspired antenna mechanics jointly with active touch speeds improve feature classification accuracy compared to conventional sensors with uniform flexural stiffness gradient by increasing tactile data sparsity and dispersion. An exploration of stiffness and damping of antenna mechanics revealed design trade-offs that influence tactile discrimination and structural stability. Through sim-to-real transfer, stiffness gradients and structured active touch motions were demonstrated on a miniature distributed soft robotic antenna, validating their effectiveness in real-world robotic systems. Taken together, this work presents a biologically grounded framework for tactile sensor design that reduces computational load and enhances adaptability.

bioengineering↗

bioRxiv2025

A live tumor fragment platform to assess immunotherapy response in core needle biopsies while addressing challenges of tumor heterogeneity

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, providing durable and even curative responses. However, most patients do not respond and current biomarkers (eg, programmed death ligand (PD-L1), mismatch repair deficiency (dMMR)/high microsatellite instability (MSI) and tumor mutational burden) lack predictive accuracy. Ex vivo profiling of patient-derived tumor fragments shows promise as a predictive biomarker but relies on substantial surgical tissue to mitigate intra-specimen heterogeneity. Innovations are needed that address these challenges, particularly where limited tissue is available in core needle biopsies (CNBs). MethodsLive tumor fragments (LTFs) were generated from 59 human tumor resections and 31 CNBs from patients enrolled in observational clinical trials (ClinicalTrials.gov identifiers: NCT05478538, NCT05520099, NCT06349642) to assess cytokine induction following ICI treatment. LTFs were encapsulated in hydrogel and cultured ex vivo for up to 72 hours. A sequential treatment strategy that applies control and treatment within the same well was used with response to ICI or CD3/CD28 assessed using a multiplex secretome assay. Viability was assessed using established metabolic assays and dynamic optical coherence microscopy. ResultsLTFs maintained viability and retained T cells responsive to stimulation throughout ex vivo culture. Multiplex immunofluorescence and immunohistochemistry showed key components of the tumor microenvironment, including relative proportions of CD4+ and CD8+ immune cell populations, were preserved. Specimens positive for PD-L1 or dMMR/MSI-high were enriched for cytokine upregulation, including T-cell response cytokines IFN{gamma} and CXCL10, after PD-1 treatment. To demonstrate clinical applicability of the sequential treatment strategy, CNBs from patients with lung, gastrointestinal or kidney cancer were profiled and differential cytokine induction in response to ICI treatment was observed. ConclusionsThe novel ex vivo platform presented is capable of detecting T-cell response to ICI treatment by using a sequential treatment strategy. This approach addresses challenges associated with cross-well heterogeneity in tissue composition and requires half as much tissue as a cross-well comparison, mitigating tissue limitations typically associated with non-surgical biopsies. Importantly, the platform is compatible with established functional assays as well as non-destructive spatial imaging, enabling researchers to characterize response to ICI longitudinally. Ongoing trials will enable clinicians to assess platform performance in predicting response to immunotherapy.

cancer biology↗

bioRxiv2025

Posterior parietal cortex activity during visually cued gait: a preliminary study

Safe gait requires visually cued (VC) step adjustments for negotiating targets and obstacles. Effective step adjustments rely on good visuospatial processing. The posterior parietal cortex (PPC) is implicated in visuospatial processing, yet empirical evidence is limited for the PPCs role during gait in humans. Increased cortical control of gait is associated with higher gait variability, a marker of gait performance and fall risk among older adults. However, the cortical underpinnings of gait variability in visually complex environments are not well established. The primary aim of this preliminary study was to assess PPC activity during VC gait and VC gait with perturbations (VCP). A secondary aim was to determine how PPC activity relates to gait variability during VC and VCP gait. Twenty-one healthy young adults completed three treadmill gait conditions at preferred speed: non-cued (NC) gait, VC gait, where stepping targets were presented in a regular pattern, and VCP gait, where stepping target positions were pseudorandomly shifted. Functional near-infrared spectroscopy quantified relative changes in deoxygenated and oxygenated hemoglobin ({Delta}HbO2) concentrations in the PPC. Inertial measurement units quantified gait variability. Moderate effects were observed for more positive {Delta}HbO2 from NC to both VC and VCP gait, likely reflecting the increased visuospatial processing demands. Stride time variability was positively correlated with PPC {Delta}HbO2 during VC gait, suggesting a potential role for the PPC in modulating temporal components of VC gait. Extending these findings to older adults will help to elucidate the PPCs role in gait adaptability and fall risk with aging.

neuroscience↗

bioRxiv2025

Mechanical and morphological features of the cockroach antenna confer flexibility, reveal a kinematic chain system and predict strain information for proprioception

A broad class of animals rely on touch sensation for perception. Among insects, the American cockroach P. americana is a touch specialist that uses a pair of soft antennae with distributed sensors to touch its environment to guide decision making. During touch, forces on the antenna can activate thousands of mechanosensors. To understand the content of this sensory information, it is critical to understand how antenna mechanics shape the transmission of contact forces. Here, we investigate the mechanical behavior and morphology of the American cockroach antenna at the individual segment level through experiments, mathematical modeling, imaging with Micro-Computed Tomography (Micro-CT), 3D reconstruction of antenna morphology, and finite element modeling (FEM). Our experimental results and model predictions reveal that the antenna flagellum bends according to a kinematic chain model, with rigid segments connected by joints. Whereas the middle region of the antenna consistently fractured under cyclic bending, the tip region remained intact under large deformations, revealing mechanical specialization along the antenna. Micro-CT imaging revealed an invagination of the exocuticle at segment intersections of the tip. To test the hypothesis that this structure can enhance flexibility and robustness, we used FEM and confirmed that the invagination allows for larger bending without structural failure (buckling). Applying FEM to a morphologically accurate kinematic chain model of the flagellum revealed the relationship between the local strain at the location of marginal sensilla and intersegment angle, predicting the information available for antenna proprioception. Taken together, these findings reveal biomechanical adaptations of insect antennae and provide a critical step toward a mechanistic understanding of touch sensation in a touch specialist. SUMMARY STATEMENTBy combining experiments, imaging and modeling, we demonstrate distinct mechanical features in the cockroach antenna and provide a framework to model the neuromechanics of the antenna in an insect touch specialist.

biophysics↗