Avery Sun

All Publications

• Mechanical memory primes cells for confined migration. Cell reports Lee, J. W., Chang, Y., Chitnis, M. S., Li, Y., Gao, X., Sun, A. R., Zhu, J., Young, J. L., Holle, A. W. 2026; 45 (4): 117267

  Abstract

  When migratory cells move between stiffness niches in vivo, they encounter confined spaces imposed by extracellular matrix (ECM) networks. Cells from one niche possess mechanosensitive adaptations that influence their response to new environments, a concept known as mechanical memory. How this memory is acquired and how it influences migratory potential in confinement remain poorly understood. Here, we combine stiffness priming using polyacrylamide hydrogels with a confinement platform to screen memory across healthy and transformed cells. Using a dose-and-passage approach, we find that cells primed on soft substrates navigate confinement more efficiently. Bulk RNA sequencing identifies NFATC2 as a transcription factor mediating mechanical memory through genetic reprogramming. Inhibition of NFATC2 confirms that it is required for memory acquisition and enhanced confined migration. Highly invasive cancer cells fail to retain mechanically induced phenotypes following cue removal, suggesting differential adaptation strategies. These findings establish mechanical memory as a cell-intrinsic regulator of confined migration.

  View details for DOI 10.1016/j.celrep.2026.117267

  View details for PubMedID 41996238

• Hybrid hydrogel-extracellular matrix scaffolds identify biochemical and mechanical signatures of cardiac ageing. Nature materials Sun, A. R., Ramli, M. F., Shen, X., Kannivadi Ramakanth, K., Chen, D., Hu, Y., Vidyasekar, P., Foo, R. S., Long, Y., Zhu, J., Ackers-Johnson, M., Young, J. L. 2025; 24 (9): 1489-1501

  Abstract

  Extracellular matrix remodelling of cardiac tissue is a key contributor to age-related cardiovascular disease and dysfunction. Such remodelling is multifaceted including changes to the biochemical composition, architecture and mechanics, clouding our understanding of how and which extracellular matrix properties contribute to a dysfunctional state. Here we describe a decellularized extracellular matrix-synthetic hydrogel hybrid scaffold that independently confers two distinct matrix properties-ligand presentation and stiffness-to cultured cells in vitro, allowing for the identification of their specific roles in cardiac ageing. The hybrid scaffold maintains native matrix composition and organization of young or aged murine cardiac tissue, whereas its mechanical properties can be independently tuned to mimic young or aged tissue stiffness. Seeding these scaffolds with murine primary cardiac fibroblasts, we identify distinct age- and matrix-dependent mechanisms of cardiac fibroblast activation, matrix remodelling and senescence. Importantly, we show that the ligand presentation of a young extracellular matrix can outweigh the profibrotic stiffness cues typically present in an aged extracellular matrix in maintaining or driving cardiac fibroblast quiescence. Ultimately, these tunable scaffolds can enable the discovery of specific extracellular targets to prevent ageing dysfunction and promote rejuvenation.

  View details for DOI 10.1038/s41563-025-02234-6

  View details for PubMedID 40506498

  View details for PubMedCentralID PMC12404999

• Isolation, Extraction, and Analysis of Cells After Confined Migration. Current protocols Gao, X., Li, Y., Lee, J. W., Zhou, J., Rangaraj, V., Sun, A. R., Young, J. L., Holle, A. W. 2025; 5 (9): e70204

  Abstract

  Cell migration through confined microenvironments is a critical biological process that underlies numerous physiological and pathological events, including immune cell trafficking, tissue morphogenesis, and cancer metastasis. Although polydimethylsiloxane-based microchannel devices have enabled detailed studies of confined migration, the efficient collection of cells post-migration for downstream molecular analyses remains a major challenge. Existing approaches often rely on harsh mechanical dissociation that compromises cell viability and integrity and do not permit in situ collection of cell lysates. To overcome these limitations, we have developed the Trap-based Recovery After Permeation (TRAP) chip, a pump-free microfluidic platform that integrates controlled confined migration with efficient post-migration cell or lysate collection. The TRAP chip incorporates microchannel arrays terminating in a precisely engineered trap region that enables gentle recovery of cells or cellular components without exposing them to high shear forces or requiring large buffer volumes. This innovation ensures the viability of recovered cells and expands the applicability of confined migration assays beyond imaging-based studies. We demonstrate that the TRAP chip facilitates the extraction of post-confinement cells for mechanical characterization, including measurement of Young's modulus, as well as the isolation of proteins and RNA suitable for downstream assays such as western blot and qPCR. The TRAP chip thus represents a significant advancement in microfluidic technologies, offering a robust, reproducible, and minimally invasive approach for studying the mechanobiology of confined migration, with broad potential for applications in basic research, cellular engineering, and translational studies where cell behavior under physical confinement is of critical importance. © 2025 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Fabrication of TRAP and control chips Basic Protocol 2: Cell seeding and live cell isolation from TRAP chips Alternate Protocol: Biomolecular extraction from TRAP chips.

  View details for DOI 10.1002/cpz1.70204

  View details for PubMedID 40981678

  View details for PubMedCentralID PMC12452805

• All the small things: Nanoscale matrix alterations in aging tissues. Current opinion in cell biology Sun, A. R., Hengst, R. M., Young, J. L. 2024; 87: 102322

  Abstract

  Cellular aging stems from multifaceted intra- and extracellular molecular changes that lead to the gradual deterioration of biological function. Altered extracellular matrix (ECM) properties that include biochemical, structural, and mechanical perturbations direct cellular- and tissue-level dysfunction. With recent advancements in high-resolution imaging modalities and nanomaterial strategies, the importance of nanoscale ECM features has come into focus. Here, we provide an updated window into micro- to nano-scale ECM properties that are altered with age and in age-related disease, and the impact these altered small-scale ECM properties have on cellular function. We anticipate future impactful research will incorporate nanoscale ECM features in the design of new biomaterials and call on the tissue biology field to work collaboratively with the nanomaterials community.

  View details for DOI 10.1016/j.ceb.2024.102322

  View details for PubMedID 38277866