Miriam B Goodman

Stanford University | SU · Department of Molecular and Cellular Physiology

The forces generated by action potentials in muscle cells shuttle blood, food and waste products throughout the luminal structures of the body. Although non-invasive electrophysiological techniques exist1, 2–3, most mechanosensors cannot access luminal structures non-invasively4, 5–6. Here we introduce non-toxic ingestible mechanosensors to enable...

Throughout history, humans have relied on plants as a source of medication, flavoring, and food. Plants synthesize large chemical libraries and release many of these compounds into the rhizosphere and atmosphere where they affect animal and microbe behavior. To survive, nematodes must have evolved the sensory capacity to distinguish plant-made smal...

Throughout history, humans have relied on plants as a source of medication, flavoring, and food. Plants synthesize large chemical libraries and release many of these compounds into the rhizosphere and atmosphere where they affect animal and microbe behavior. To survive, nematodes must have evolved the sensory capacity to distinguish plant-made smal...

This Viewpoint, which accompanies a Special Issue focusing on membrane mechanosensors, discusses unifying and unique features of both established and emerging mechanosensitive (MS) membrane proteins, their distribution across protein families and phyla, and current and future challenges in the study of these important proteins and their partners. M...

The visualization of mechanical stress distribution in specific molecular networks within a living and physiologically active cell or animal remains a formidable challenge in mechanobiology. The advent of fluorescence-resonance energy transfer (FRET)-based molecular tension sensors overcame a significant hurdle that now enables us to address previo...

Head injury simulations predict the occurrence of traumatic brain injury by placing a threshold on the calculated strains for axon tracts within the brain. However, a current roadblock to accurate injury prediction is the selection of an appropriate axon damage threshold. While several computational studies have used models of the axon cytoskeleton...

The sense of touch is conferred by the conjoint function of somatosensory neurons and skin cells. These cells meet across a gap filled by a basal lamina, an ancient structure found in all metazoans. Using Caenorhabditis elegans nematodes, we show that mechanosensory complexes essential for touch sensation reside at this interface and contain lamini...

Upconverting nanoparticles (UCNPs) are an emerging platform for mechanical force sensing at the nanometer scale. An outstanding challenge in realizing nanometer-scale mechano-sensitive UCNPs is maintaining a high mechanical force responsivity in conjunction with bright optical emission. This Letter reports mechano-sensing UCNPs based on the lanthan...

The degenerin channels, epithelial sodium channels, and acid-sensing ion channels (DEG/ENaC/ASICs) play important roles in sensing mechanical stimuli, regulating salt homeostasis, and responding to acidification in the nervous system. They have two transmembrane domains separated by a large extracellular domain and are believed to assemble as homom...

Cutaneous mechanosensory neurons are activated by mechanical loads applied to the skin, and these stimuli are proposed to generate mechanical strain within sensory neurons. Using a microfluidic device to deliver controlled stimuli to intact animals and large, immobile, and fluorescent protein-tagged mitochondria as fiducial markers in the touch rec...

The degenerin channels, epithelial sodium channels, and acid-sensing ion channels (DEG/ENaC/ASICs) play important roles in sensing mechanical stimuli, regulating salt homeostasis, and responding to acidification in the nervous system. They have two transmembrane domains separated by a large extracellular domain and are believed to assemble as homom...

We measure the color ratio-metric response of alkaline-earth rare-earth upconverting nanoparticles with a diamond anvil cell. We find ensembles of SrLuF particles detect 32.8 MPa in pressure change corresponding to 24 nN of force.

Cutaneous mechanosensory neurons are activated by mechanical loads applied to the skin likely to result in local mechanical strain within sensory neurons. Using a microfluidics device to deliver controlled stimuli to intact animals and large, immobile and fluorescent protein-tagged mitochondria as fiducial markers in the touch receptor neurons (TRN...

Neurons convert synaptic or sensory inputs into cellular outputs. It is not well understood how a single neuron senses, processes multiple stimuli, and generates distinct neuronal outcomes. Here, we describe the mechanism by which the C. elegans PVD neurons sense two mechanical stimuli: external touch and proprioceptive body movement. These two sti...

Touch deforms, or strains, the skin beyond the immediate point of contact. The spatiotemporal nature of the touch-induced strain fields depend on the mechanical properties of the skin and the tissues below. Somatosensory neurons that sense touch branch out within the skin and rely on a set of mechano-electrical transduction channels distributed wit...

Touch sensation hinges on force transfer across the skin and activation of mechanosensitive ion channels along the somatosensory neurons that invade the skin. This skin-nerve sensory system demands a quantitative model that spans the application of mechanical loads to channel activation. Unlike prior models of the dynamic responses of touch recepto...

Upconverting nanoparticles (UCNPs) are promising tools for background-free imaging and sensing. However, their usefulness for in vivo applications depends on their biocompatibility, which we define by their optical performance in biological environments and their toxicity in living organisms. For UCNPs with a ratiometric color response to mechanica...

Caenorhabditis elegans lives in a complex habitat in which they routinely experience large fluctuations in temperature, and encounter physical obstacles that vary in size and composition. Their habitat is shared by other nematodes, by beneficial and harmful bacteria, and nematode-trapping fungi. Not surprisingly, these nematodes can detect and disc...

Gentle touch sensation in mammals depends on synaptic transmission from primary sensory cells (Merkel cells) to secondary sensory neurons. Hoffman et al. (2018) identify norepinephrine and β2-adrendergic receptors as the neurotransmitter-receptor pair responsible for sustained touch responses. The findings may deepen understanding of how drugs affe...

The sense of touch hinges on tissues transducing stimuli applied to the skin and somatosensory neurons converting mechanical inputs into currents. Like mammalian Pacinian corpuscles, the light-touch response of the prime model organism C. elegans adapts rapidly, and is symmetrically activated by the onset and offset of a step indentation. Here, we...

Sensory neurons embedded in skin are responsible for the sense of touch. In humans and other mammals, touch sensation depends on thousands of diverse somatosensory neurons. By contrast, Caenorhabditis elegans nematodes have six gentle touch receptor neurons linked to simple behaviors. The classical touch assay uses an eyebrow hair to stimulate free...

The ability to adapt behavior to environmental fluctuations is critical for survival of organisms ranging from invertebrates to mammals. Caenorhabditis elegans can learn to avoid sodium chloride when it is paired with starvation. This behavior may help animals avoid areas without food. While some genes have been implicated in this salt aversive lea...

The nematode C. elegans exhibits complex thermal experience-dependent navigation behaviors in response to environmental temperature changes of as little as 0.01°C over a > 10°C temperature range. The remarkable thermosensory abilities of this animal are mediated primarily via the single pair of AFD sensory neurons in its head. In this review, we de...

One central goal of mechanobiology is to understand the reciprocal effect of mechanical stress on proteins and cells. Despite its importance, the influence of mechanical stress on cellular function is still poorly understood. In part, this knowledge gap exists because few tools enable simultaneous deformation of tissue and cells, imaging of cellula...

Focused ultrasound has been shown to stimulate excitable cells, but the biophysical mechanisms behind this phenomenon remain poorly understood. To provide additional insight, we devised a behavioral-genetic assay applied to the well-characterized nervous system of C. elegans nematodes. We found that pulsed ultrasound elicits robust reversal behavio...

The ability to adapt behavior to environmental fluctuations is critical for survival of organisms ranging from invertebrates to mammals. Caenorhabditis elegans can learn to avoid sodium chloride when it is paired with starvation. This behavior is likely advantageous to avoid areas without food. While some genes have been implicated in this salt ave...

For decades, Caenorhabditis elegans roundworms have been used to study the sense of touch, and this work has been facilitated by a simple behavioral assay for touch sensation. To perform this classical assay, an experimenter uses an eyebrow hair to gently touch a moving worm and observes whether or not the worm reverses direction. We used two exper...

All touch events for volunteer G. Touch events are sorted from largest force (top left) to smallest force (bottom right). Upon unloading of most touches, the cantilever rings. The stimuli delivered by subjects was generally between 80 ms and 1 s in duration and unimodal (one peak) with a slower loading rate and quick unloading. There were some touc...

Raw force data. These text files contain raw voltage data collected as described in the Methods section. The analysis scripts in S1 Analysis Code were used to process these data. (ZIP)

Code used to analyze force data. The matlab code used to do all data analysis is contained in this zip file. Also requires S2 Data. (ZIP)

Representative video of touch assay. This is the full video from which the images in panel A of Fig 3. (AVI)

Peak forces for all touches from volunteers. CSV file containing the maximum force for all 30 touches from each volunteer. (CSV)

New tools for applying force to animals, tissues, and cells are critically needed in order to advance the field of mechanobiology, as few existing tools enable simultaneous imaging of tissue and cell deformation as well as cellular activity in live animals. Here, we introduce a novel microfluidic device that enables high-resolution optical imaging...

Adapting behavior to thermal cues is essential for animal growth and survival. Indeed, each and every biological and biochemical process is profoundly affected by temperature and its extremes can cause irreversible damage. Hence, animals have developed thermotransduction mechanisms to detect and encode thermal information in the nervous system and...

Microtubules contribute to many cellular processes, including transport, signaling, and chromosome separation during cell division. They comprise αβ‑tubulin heterodimers arranged into linear protofilaments and assembled into tubes. Eukaryotes express multiple tubulin isoforms, and there has been a longstanding debate as to whether the isoforms are...

Microtubules contribute to many cellular processes, including transport, signaling, and chromosome separation during cell division (Kapitein and Hoogenraad, 2015). They are comprised of αβ-tubulin heterodimers arranged into linear protofilaments and assembled into tubes. Eukaryotes express multiple tubulin isoforms (Gogonea et al. , 1999), and ther...

Significance Recordings from Pacinian corpuscles in the 1960s showed that touch elicits symmetric activation followed by rapid adaptation. Sinusoidal stimulation resulted in frequency doubling within a sensitive frequency band, suggesting that these receptors function as frequency-tuned vibration sensors. At the time, the surrounding lamellar capsu...

Organisms as diverse as microbes, roundworms, insects, and mammals detect and respond to applied force. In animals, this ability depends on ionotropic force receptors, known as mechanoelectrical transduction (MeT) channels, that are expressed by specialized mechanoreceptor cells embedded in diverse tissues and distributed throughout the body. These...

Statistical analysis of FRET data. DOI: http://dx.doi.org/10.7554/eLife.06565.015

mec-8 tiling array data. (A) Gene Regions. Gene regions determined to be differentially expressed in mec-8 animals as compared with wild type. Genes for which all exons were up or down regulated are in bold. Region indicates the specific exons or introns of a transcript that were up or down regulated in mec-8 animals. Note that exon or intron numbe...

Percentage of Pin Animals. DOI: http://dx.doi.org/10.7554/eLife.06565.014

The sense of touch informs us of the physical properties of our surroundings and is a critical aspect of communication. Before touches are perceived, mechanical signals are transmitted quickly and reliably from the skin's surface to mechano-electrical transduction channels embedded within specialized sensory neurons. We are just beginning to unders...

Sensory adaptation represents a form of experience-dependent plasticity that allows neurons to retain high sensitivity over a broad dynamic range. The mechanisms by which sensory neuron responses are altered on different timescales during adaptation are unclear. The threshold for temperature-evoked activity in the AFD thermosensory neurons (T(∗)AFD...

Through encounters with predators, competitors, and noxious stimuli, animals have evolved defensive responses that minimize injury and are essential for survival. Physiological adaptation modulates the stimulus intensities that trigger such nocifensive behaviors, but the molecular networks that define their operating range are largely unknown. Here...

A trio of papers has resolved an outstanding controversy regarding the function of Merkel cells and their afferent nerve fiber partners. Merkel cells sense mechanical stimuli (through Piezo2), fire action potentials, and are sufficient to activate downstream sensory neurons.

This chapter describes four different protocols used to assay thermotaxis navigation behavior of single, or populations of, C. elegans hermaphrodites on spatial thermal gradients within the physiological temperature range (15-25°C). A method to assay avoidance of noxious temperatures is also described.

The ability to sense and respond to mechanical stimuli emanates from sensory neurons and is shared by most, if not all, animals. Exactly how such neurons receive and distribute mechanical signals during touch sensation remains mysterious. Here, we show that sensation of mechanical forces depends on a continuous, pre-stressed spectrin cytoskeleton i...

Significance The nematode Caenorhabditis elegans offers the opportunity to map complex behaviors to the specific roles of each neuron in a 302-neuron nervous system. Thermotaxis is a complex behavior where the worm inverts the behavioral mode—positive thermotaxis up gradients or negative thermotaxis down gradients—to move toward a remembered temper...

Many somatosensory neurons have evolved specialized molecular sensors that convert mechanical stress into behavioral responses. The genetics, development and physiology of the touch receptor neurons (TRNs) in Caenorhabditis elegans nematodes are especially well characterized and this animal has the particular advantage that the TRNs can be studied...

Mechano-electrical transduction (MeT) channels embedded in neuronal cell membranes are essential for touch and proprioception. Little is understood about the interplay between native MeT channels and membrane phospholipids, in part because few techniques are available for altering plasma membrane composition in vivo. Here, we leverage genetic disse...

Mechanoelectrical transduction (MeT) channels embedded in neuronal cell membranes are essential for touch and proprioception. Little is understood about the interplay between native MeT channels and membrane phospholipids, in part because few techniques are available for altering plasma membrane composition in vivo. Here, we leverage genetic dissec...

The evolution of metazoans from their choanoflagellate-like unicellular ancestor coincided with the acquisition of novel biological functions to support a multicellular lifestyle, and eventually, the unique cellular and physiological demands of differentiated cell types such as those forming the nervous, muscle and immune systems. In an effort to u...

Touch is enabled by mechanoreceptor neurons in the skin and plays an essential role in our everyday lives, but is among the least understood of our five basic senses. Force applied to the skin deforms these neurons and activates ion channels within them. Despite the importance of the mechanics of the skin in determining mechanoreceptor neuron defor...

Touch, proprioception, and blood pressure regulation rely on mechanoreceptor neurons and mechano-electrical transduction (MeT) channels to convert mechanical cues into electrical signals. The protein partners that form native MeT channels are known only for a small group of mechanoreceptor neurons, including the touch receptor neurons responsible f...

Patch-clamp electrophysiology is a technique of choice for the biophysical analysis of the function of nerve, muscle, and synapse in Caenorhabditis elegans nematodes. Considerable technical progress has been made in C. elegans electrophysiology in the decade since the initial publication of this technique. Today, most, if not all, electrophysiologi...

The founding members of the superfamily of DEG/ENaC ion channel proteins are C. elegans proteins that form mechanosensitive channels in touch and pain receptors. For more than a decade, the research community has used mutagenesis to identify motifs that regulate gating. This review integrates insight derived from unbiased in vivo mutagenesis screen...

Doublecortin-domain containing (DCDC) genes play key roles in the normal and pathological development of the human brain cortex. The origin of the cellular specialisation and the functional redundancy of these microtubule (MT)-associated proteins (MAPs), especially those of Doublecortin (DCX) and Doublecortin-like kinase (DCLKs) genes, is still unc...

Microtubules are built from linear polymers of α-β tubulin dimers (protofilaments) that form a tubular quinary structure. Microtubules assembled from purified tubulin in vitro contain between 10 and 16 protofilaments; however, such structural polymorphisms are not found in cells. This discrepancy implies that factors other than tubulin constrain mi...

Every moment of every day, our skin and its embedded sensory neurons are bombarded with mechanical cues that we experience as pleasant or painful. Knowing the difference between innocuous and noxious mechanical stimuli is critical for survival and relies on the function of mechanoreceptor neurons that vary in their size, shape, and sensitivity. The...

Touch is among the least understood of our senses despite its importance in our daily lives. In the model organism C. elegans, gentle touch is detected by six touch receptor neurons situated in the outer shell of the animal. Force applied to the body is filtered by the outer shell (cuticle, hypodermis and body wall muscles) of the body, locally str...

Alternative splicing is critical for diversifying eukaryotic proteomes, but the rules governing and coordinating splicing events among multiple alternate splice sites within individual genes are not well understood. We developed a quantitative PCR-based strategy to quantify the expression of the 12 transcripts encoded by the Caenorhabditis elegans...

Most human genes contain multiple alternative splice sites believed to extend the complexity and diversity of the proteome. However, little is known about how interactions among alternative exons regulate protein function. We used the Caenorhabditis elegans slo-1 large-conductance calcium and voltage-activated potassium (BK) channel gene, which con...

Many nociceptors detect mechanical cues, but the ion channels responsible for mechanotransduction in these sensory neurons remain obscure. Using in vivo recordings and genetic dissection, we identified the DEG/ENaC protein, DEG-1, as the major mechanotransduction channel in ASH, a polymodal nociceptor in Caenorhabditis elegans. But DEG-1 is not the...

Gentle touch sensation in Caenorhabditis elegans is mediated by the MEC-4/MEC-10 channel complex, which is expressed exclusively in six touch receptor neurons (TRNs). The complex contains two pore-forming subunits, MEC-4 and MEC-10, as well as the accessory subunits MEC-2, MEC-6, and UNC-24. MEC-4 is essential for channel function, but beyond its r...

Body mechanics in the nematode Caenorhabditis elegans are central to both mechanosensation and locomotion. Previous work revealed that the mechanics of the outer shell, rather than internal hydrostatic pressure, dominates stiffness. This shell is comprised of the cuticle and the body wall muscles, either of which could contribute to the body mechan...

We present a microelectromechanical device-based tool, namely, a force-clamp system that sets or "clamps" the scaled force and can apply designed loading profiles (e.g., constant, sinusoidal) of a desired magnitude. The system implements a piezoresistive cantilever as a force sensor and the built-in capacitive sensor of a piezoelectric actuator as...

The ability to avoid noxious extremes of hot and cold is critical for survival and depends on thermal nociception. The TRPV subset of transient receptor potential (TRP) channels is heat activated and proposed to be responsible for heat detection in vertebrates and fruit flies. To gain insight into the genetic and neural basis of thermal nociception...