About

Esther Gomez Waltemeyer is a Mid-Career Biotechnology Professor and Associate Department Head in the Department of Chemical Engineering at Penn State University. Her research areas include Biotechnology and Synthetic Biology, with a focus on interfaces and surfaces. Her interest areas involve mechanobiology and the structural characterization of biological assemblies using advanced X-ray scattering tools. Her work explores the interplay of chemical and mechanical signals in controlling cell behavior and disease progression, as well as the characterization of biological assemblies such as plant cell walls and proteins in solution. Dr. Gomez has contributed to the understanding of biological systems through her extensive research and publications in the field of biotechnology and bioengineering.

Research topics

• Materials science
• Chemistry
• Biology
• Cell biology
• Nanotechnology

Selected publications

• Editorial: Mechanopathology: unraveling the mechanical forces driving disease mechanisms

  Frontiers in Cell and Developmental Biology · 2026-02-12

  articleOpen access

  Editorial: Mechanopathology: Unraveling the Mechanical Forces Driving Disease Mechanisms Bertocchi C., Rizzuto E, Gomez E.W., Peruzzi B.Mechanical forces are essential regulators of cellular and tissue function, actively shaping behavior, gene expression, and tissue organization. When altered, these physical cues, such as tissue stiffness, shear stress, and mechanical strain, can drive pathological scenarios. This dynamic interplay defines mechanopathology, where abnormal mechanical environments and defective mechanosensing, alongside biochemical and genetic factors, directly contribute to disease initiation and progression. This Research Topic integrates five multidisciplinary contributions that illustrate how mechanical forces influence molecular and cellular mechanisms across pathological contexts, including inflammation, vascular and lymphatic biology, cancer, and musculoskeletal degeneration, while highlighting their potential to inspire innovative diagnostic and therapeutic strategies. A unifying theme emerges from these studies: mechanical cues are not merely modulators of disease but active drivers that integrate with biochemical signaling to shape pathological outcomes. At the cellular scale, the actin cytoskeleton, dynamically regulated by polymerization complexes such as the actin-related protein 2/3 (Arp2/3) complex, represents a primary interface between mechanical forces and intracellular signaling. In their comprehensive review, Xing et al. link Arp2/3-mediated-actin polymerization dynamics to immune cell migration, phagocytosis, and cytokine production. Their findings reveal that cytoskeletal remodeling, driven by Arp2/3, enables immune cells to reorganize actin into branched networks, critical for forming lamellipodia and filopodia that interact with the extracellular matrix (ECM). This interaction is not passive: the ECM's physical properties, such as stiffness and topography, feedback to modulate Arp2/3 activity, creating a bidirectional mechanotransduction loop that fine-tunes immune responses. For example, in stiffened ECM environments, such as those found in fibrotic tissues or tumors, Arp2/3 activation is enhanced, leading to increased immune cell infiltration and pro-inflammatory cytokine release, which further remodels the ECM. Intriguingly, this principle extends into vascular and lymphatic biology, where cells are constantly exposed to dynamic physical forces. Xu et al. provide experimental evidence of how ECM stiffness modulates the proliferation and migratory behaviour of lymphatic endothelial cells through the mechanosensitive protein FAT (FAT Atypical Cadherin) 1. Their findings reveal that FAT1 acts as a pivotal mechanosensory, translating ECM stiffness into intracellular signals that regulate lymphatic endothelial cell behaviour and tissue homeostasis. This mechanotransduction pathway underscores how altered tissue mechanics, whether due to fibrosis, chronic inflammation, or tumor growth, actively drive pathological processes, reinforcing the notion that ECM physical properties are not merely consequences of disease, but central regulators of cellular behaviour and tissue homeostasis. This is best embodied in cancer, where abnormal tissue mechanics (i.e., ECM stiffness, solid stress, and interstitial pressure) are a hallmark of the tumor microenvironment (TME). In their review, Angeli et al. explore how, in solid tumors such as breast carcinoma and melanoma, physical characteristics of the TME, orchestrate tumor growth, invasion, immune cell infiltration, and treatment resistance. These interconnected physical forces drive tumor progression by activating mechanosensitive pathways, including Yes-associated protein (YAP)/transcriptional coactivator with a PDZ-binding domain (TAZ) signaling and integrin-mediated cytoskeletal reorganization. Within this stiffened, pressurized TME vascular and lymphatic compression exacerbates hypoxia and immune evasion, while also triggering oncogenic programs that enhance cell survival, migration, and resistance to therapy. YAP/TAZ, acting as central mechanotransducers, amplify these effects by upregulating targets like cysteine-rich angiogenic inducer 61 (CYR61) and connective tissue growth factor (CTGF) and modulating immune checkpoint expression (e.g., Programmed Death Ligand 1, PD-L1), thus linking ECM mechanics to both tumor cell autonomy and immune suppression. This mechanistic framework underscores the translational potential of targeting mechanical cues, through YAP/TAZ inhibition, anti-fibrotic agents, or Focal Adhesion Kinase (FAK)/Piezo1 blockade, to disrupt the pro-tumorigenic feedback loop between the ECM and cancer cells. Expanding on these observations, Zhang et al. offer a comprehensive review of mechanosensitive ion channels (such as Piezo and transient receptor potential (TRP) family members) focusing on their role in osteoarthritis pathogenesis. The authors summarize current knowledge on these channels emphasizing their ability to convert mechanical stimuli (e.g., compressive stress, shear forces) into intracellular signals that drive inflammation, ECM degradation, and pain sensitization. Piezo1/2 and TRPV4, upregulated in osteoarthritic chondrocytes, trigger calcium influx, matrix metalloproteinases (MMP)/ tissue inhibitors of metalloproteinases (TIMP) imbalance, and chondrocyte senescence, thereby accelerating cartilage breakdown. Chondrocyte-specific knockout of Piezo1 and Piezo2 in murine models attenuates posttraumatic osteoarthritis progression, highlighting these channels as therapeutic targets for both structural preservation and symptom relief. In the context of post-traumatic osteoarthritis (PTOA), Miao et al. investigate the mechanosensitive protein Anthrax toxin receptor (ANTXR)1 revealing its complementary role in maintaining cartilage homeostasis. Their work demonstrates that ANTXR1 interacts with the Wnt co-receptor (LRP6) to maintain cartilage homeostasis under mechanical stress, and that its deficiency aggravates cartilage degeneration following injury. Together, these studies frame osteoarthritis as a disease of dysregulated mechanotransduction, where Piezo1/2/TRPV4 drive degradation and inflammation, and ANTXR1 supports cartilage integrity, offering dual therapeutic avenues: inhibiting ion channels to block catabolic pathways, and restoring ANTXR1 function to promote anabolic repair. Taken together, the articles in this Research Topic converge on several unifying principles. First, mechanical forces are integrated within cellular signaling networks, regulating processes from cytoskeletal dynamics to ion channel activity and gene expression. Second, pathological alterations in tissue mechanics actively drive disease progression, as demonstrated across inflammation, vascular biology, osteoarthritis, and cancer. Third, these mechanotransduction pathways offer targets for therapeutic intervention, where mechanical and biochemical signals intersect. In summary, this Research Topic positions mechanopathology as a unifying framework for understanding disease, reinforcing the importance of mechanics alongside genetic and biochemical factors.

  PublisherOA PDFDOI

• Automated TEM Reveals Intercrystalline Correlations of Conjugated Polymers

  Macromolecules · 2026-02-09

  articleOpen accessCorresponding

  Transmission electron microscopy (TEM) continues to transform polymer science by revealing key aspects of chain packing, phase separation and nanoscale structure. The development of instrumentation and data analyses tools is driving the field forward and enabling new experiments. Here, we use automated high-resolution TEM (HRTEM) and image processing to identify the structure of a conjugated polymer used in organic electronics. Analysis of more than 600 HRTEM images reveals lattice parameters and orientation correlations between crystals, including the preferred alignment of neighboring crystals along the same crystallographic direction that is likely the result of liquid crystalline order.

  PublisherDOI

• Cryogenic transmission electron microscopy reveals assembly and nanostructure of PEDOT:PSS

  Nature Communications · 2026-02-10

  articleOpen access

  Soft and conducting organic materials are ideal candidates for stretchable bioelectronics and wearable devices. Despite recent advances, our understanding of conducting polymer nanostructures and how they arise remains incomplete, given the limited high-resolution studies and molecular-level descriptions of these systems. Here, we employ cryogenic transmission electron microscopy (cryo-EM) to investigate the evolution of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) morphology in solution and the resulting solid state structure in the presence of ionic and molecular additives. Our results reveal the formation of heterostructural elongated fibers consisting of PEDOT:PSS micelles in solution. Cryo-EM further reveals that additives increase the number of fibrils, in addition to inducing the formation of crystalline domains. We observe that fibril and crystalline phases in solutions act as a template for the growth of these nanostructures in the solid state. Furthermore, exploiting cryo-EM reveals the role of solid-liquid interactions in PEDOT:PSS through the imaging of PEDOT:PSS nanostructures after the hydration of thin films. Hydration leads to the swelling of heterostructural fibers while reducing the crystalline domain size. Such behavior explains the mechanical robustness of PEDOT:PSS thin films processed with various additives as well as the high electrical conductivity of PEDOT:PSS in applications such as organic electorchemical transistors. Soft and conducting organic materials are promising for electronic devices, though their nanostructures are not fully understood, due to the lack of high resolution real spacing imaging of these complex systems. Here the authors use cryogenic transmission electron microscopy methods to investigate the morphology of PEDOT:PSS in the presence of additives and upon hydration.

  PublisherOA PDFDOI

• Empirical evidence that glucan-interacting amino acid side chains within the transmembrane channel collectively facilitate cellulose synthase function

  Plant Molecular Biology · 2025-07-09 · 1 citations

  articleOpen access

  The fundamental mechanism of cellulose synthesis is widely conserved across Kingdoms and depends on cellulose synthases, which are processive, dual-function, family 2 glycosyltransferases (GT-2). These enzymes polymerize glucose on the cytoplasmic side of the plasma membrane and export the glucan chain to the cell surface through an integral transmembrane (TM) channel. Structural studies of active plant cellulose synthases (CESAs) have revealed interactions between the nascent glucan chain and the side chains of polar, charged, and aromatic amino acid residues that line the TM channel. However, the functional consequences of modifying these side chains have not been tested in vivo in CESAs or other processive GT-2s. To test this, we used an established in vivo assay based on genetic complementation of CESA5 in the moss, Physcomitrium patens. For accurate prediction of glucan-interacting amino acid residues, we generated a complete homotrimeric molecular model of PpCESA5 using a combination of homology and de novo modeling. All-atom molecular dynamics-based analyses of contact metrics and interaction energy identified 23 amino acid residues with high propensity to interact with the nascent glucan chain within the TM channel or on the apoplastic surface of PpCESA5. Mutating any one of 18 of these amino acid residues to alanine, thereby removing their side chains, abolished or impaired CESA function, with the strongest effects observed upon the loss of charged amino acid side chains. This provides direct evidence to support the hypothesis that multiple amino acid residues collectively maintain a smooth energy landscape within the TM channel to facilitate glucan translocation.

  PublisherDOI

• The Impact of Applied Improvisation on Undergraduate Engineering Students’ Professional Development

  2025-01-01

  articleOpen access

  Integrating humanities and arts into STEM has been suggested to better prepare students for the workforce. Studies have shown that improvisation (abbreviated as improv), an educational program from humanities and arts, can potentially improve engineering pedagogy and learning. However, little is known about improv’s impact on developing undergraduate engineering students’ growth mindset. Also, more

  PublisherOA PDFDOI

• Matrix Stiffness Regulates <scp>TGFβ1</scp> ‐Induced <scp>αSMA</scp> Expression via a G9a‐ <scp>LATS</scp> ‐ <scp>YAP</scp> Signaling Cascade

  FASEB BioAdvances · 2025-07-01 · 1 citations

  articleOpen accessSenior authorCorresponding

  Extracellular matrix stiffness is enhanced in cancer and fibrosis; however, there is limited knowledge on how matrix mechanics modulate expression and signaling of the methyltransferase G9a. Here, we show that matrix stiffness and transforming growth factor (TGF)-β1 signaling together regulate G9a expression and the levels of the histone mark H3K9me2. Suppressing the activity and expression of G9a attenuates TGFβ1-induced alpha smooth muscle actin (αSMA) and N-cadherin expression and cell morphology changes in mammary epithelial cells cultured on stiff substrata. Knockdown of G9a increases the expression of large tumor suppressor kinase 2 (LATS2) and decreases the nuclear localization of yes associated protein (YAP). Furthermore, inhibition of LATS promotes an increase in YAP nuclear localization and αSMA expression, while inhibition of YAP attenuates αSMA expression. Overall, our findings indicate that a G9a-LATS-YAP signaling cascade regulates mammary epithelial cell response to matrix stiffness and TGFβ1.

  PublisherOA PDFDOI

• Contributors

  Elsevier eBooks · 2024-01-01

  book-chapter
  PublisherDOI

• Epithelial–Mesenchymal Plasticity and Epigenetic Heterogeneity in Cancer

  Cancers · 2024-09-27 · 9 citations

  reviewOpen accessSenior authorCorresponding

  The tumor microenvironment comprises various cell types and experiences dynamic alterations in physical and mechanical properties as cancer progresses. Intratumoral heterogeneity is associated with poor prognosis and poses therapeutic challenges, and recent studies have begun to identify the cellular mechanisms that contribute to phenotypic diversity within tumors. This review will describe epithelial-mesenchymal (E/M) plasticity and its contribution to phenotypic heterogeneity in tumors as well as how epigenetic factors, such as histone modifications, histone modifying enzymes, DNA methylation, and chromatin remodeling, regulate and maintain E/M phenotypes. This review will also report how mechanical properties vary across tumors and regulate epigenetic modifications and E/M plasticity. Finally, it highlights how intratumoral heterogeneity impacts therapeutic efficacy and provides potential therapeutic targets to improve cancer treatments.

  PublisherOA PDFDOI

• Matrix polysaccharides affect preferred orientation of cellulose crystals in primary cell walls

  Cellulose · 2024-01-09 · 3 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Dynamic Structural Change of Plant Epidermal Cell Walls under Strain

  Small · 2024-02-22 · 13 citations

  articleOpen accessCorresponding

  The molecular foundations of epidermal cell wall mechanics are critical for understanding structure-function relationships of primary cell walls in plants and facilitating the design of bioinspired materials. To uncover the molecular mechanisms regulating the high extensibility and strength of the cell wall, the onion epidermal wall is stretched uniaxially to various strains and cell wall structures from mesoscale to atomic scale are characterized. Upon longitudinal stretching to high strain, epidermal walls contract in the transverse direction, resulting in a reduced area. Atomic force microscopy shows that cellulose microfibrils exhibit orientation-dependent rearrangements at high strains: longitudinal microfibrils are straightened out and become highly ordered, while transverse microfibrils curve and kink. Small-angle X-ray scattering detects a 7.4 nm spacing aligned along the stretch direction at high strain, which is attributed to distances between individual cellulose microfibrils. Furthermore, wide-angle X-ray scattering reveals a widening of (004) lattice spacing and contraction of (200) lattice spacing in longitudinally aligned cellulose microfibrils at high strain, which implies longitudinal stretching of the cellulose crystal. These findings provide molecular insights into the ability of the wall to bear additional load after yielding: the aggregation of longitudinal microfibrils impedes sliding and enables further stretching of the cellulose to bear increased loads.

  PublisherOA PDFDOI

Frequent coauthors

• Nitash P. Balsara

  Lawrence Berkeley National Laboratory

  89 shared

• Esther W. Gomez

  Pennsylvania State University

  52 shared

• Youngmin Lee

  Oral Roberts University

  45 shared

• Scott T. Milner

  National Society of Professional Engineers

  30 shared

• Alexander Hexemer

  Lawrence Berkeley National Laboratory

  30 shared

• Kiarash Vakhshouri

  Pennsylvania State University

  27 shared

• Timothy J. Rappl

  University of California, Berkeley

  26 shared

• Andrew M. Minor

  University of California, Berkeley

  26 shared

Labs

• Chemical EngineeringPI

Education

• PhD, Chemical Engineering

  University of California Berkeley

  2007

• BS, Chemical Engineering

  University of Florida

  2002