When a molecule arrives at a cell's outer membrane, the membrane creates a pouch around the molecule that protrudes inward. Directed by a protein called dynamin, the pouch then gets pinched off to form a vesicle that carries the molecule to the right place inside the cell. To better understand how dynamin performs its vital pouch-pinching role, researchers determined its structure. Based on the structure, they proposed that a dynamin "collar" at the pouch's base twists ever tighter until the vesicle pops free. Because cells absorb many drugs through vesicles, the discovery could lead to new drug delivery methods.

A 3D model of the human endoplasmic reticulum membrane protein complex (EMC) that identifies its nine essential subunits. The EMC plays an important role in making membrane proteins, which are essential for all cellular processes. This is the first atomic-level depiction of the EMC. Its structure was obtained using single-particle cryo-electron microscopy.

Just as our bodies rely on bones for structural support, our cells rely on a cellular skeleton. In addition to helping cells keep their shape, this cytoskeleton transports material within cells and coordinates cell division. One component of the cytoskeleton is a protein called tubulin, shown here as thin strands.

This image was part of the Life: Magnified exhibit that ran from June 3, 2014, to January 21, 2015, at Dulles International Airport.

A 20-µm thick section of mouse midbrain. The nerve cells are transparent and weren’t stained. Instead, the color is generated by interaction of white polarized light with the molecules in the cells and indicates their orientation.

The image was obtained with a polychromatic polarizing microscope that shows the polychromatic birefringent image with hue corresponding to the slow axis orientation. More information about the microscopy that produced this image can be found in the Scientific Reports paper “Polychromatic Polarization Microscope: Bringing Colors to a Colorless World” by Shribak.

The two large, central, round shapes are ovaries from a typical fruit fly (Drosophila melanogaster). The small butterfly-like structures surrounding them are fruit fly ovaries where researchers suppressed the expression of a gene that controls microtubule polymerization and is necessary for normal development. This image was captured using a confocal laser scanning microscope.

Related to image 6807.

If a picture is worth a thousand words, what's a movie worth? For researchers studying cell migration, a "documentary" of fruit fly cells (bright green) traversing an egg chamber could answer longstanding questions about cell movement. See 2315 for video.

A blue laser beam turns on a protein that helps this human cancer cell move. Responding to the stimulus, the protein, called Rac1, first creates ruffles at the edge of the cell. Then it stretches the cell forward, following the light like a horse trotting after a carrot on a stick. This new light-based approach can turn Rac1 (and potentially many other proteins) on and off at exact times and places in living cells. By manipulating a protein that controls movement, the technique also offers a new tool to study embryonic development, nerve regeneration and cancer.

The human skin cells pictured contain genetic modifications that make them pluripotent, essentially equivalent to embryonic stem cells. A scientific team from the University of Wisconsin-Madison including researchers Junying Yu, James Thomson, and their colleagues produced the transformation by introducing a set of four genes into human fibroblasts, skin cells that are easy to obtain and grow in culture.

Cells move forward with lamellipodia and filopodia supported by networks and bundles of actin filaments. Proper, controlled cell movement is a complex process. Recent research has shown that an actin-polymerizing factor called the Arp2/3 complex is the key component of the actin polymerization engine that drives amoeboid cell motility. ARPC3, a component of the Arp2/3 complex, plays a critical role in actin nucleation. In this photo, the ARPC3-/- fibroblast cells were fixed and stained with Alexa 546 phalloidin for F-actin (red), mDia1 (green), and DAPI to visualize the nucleus (blue). In ARPC3-/- fibroblast cells, mDia1 is localized at the tips of the filopodia-like structures. Related to images 3328, 3329, 3330, 3332, and 3333.

Moving protein or other molecules to specific cells to treat or examine them has been a major biological challenge. Scientists have now developed a technique for delivering chemicals to individual cells. The approach involves gold nanowires that, for example, can carry tumor-killing proteins. The advance was possible after researchers developed electric tweezers that could manipulate gold nanowires to help deliver drugs to single cells.

This movie shows the manipulation of the nanowires for drug delivery to a single cell. To learn more about this technique, see this post in the Computing Life series.

A light microscope image of a cell from the endosperm of an African globe lily (Scadoxus katherinae). This is one frame of a time-lapse sequence that shows cell division in action. The lily is considered a good organism for studying cell division because its chromosomes are much thicker and easier to see than human ones. Staining shows microtubules in red and chromosomes in blue. Here, condensed chromosomes are clearly visible and are starting to line up.

Related to images 1010, 1011, 1012, 1013, 1014, 1015, 1017, 1018, 1019, and 1021.

A rendering of an activity biosensor image overlaid with a cell-centered frame of reference used for image analysis of signal transduction. This is an example of NIH-supported research on single-cell analysis. Related to 2798 , 2799, 2800, 2801 and 2803.

The plasma membrane is a cell's protective barrier. See image 2523 for an unlabeled version of this illustration. Featured in The Chemistry of Health.

The small intestine is where most of our nutrients from the food we eat are absorbed into the bloodstream. The walls of the intestine contain small finger-like projections called villi which increase the organ's surface area, enhancing nutrient absorption. It consists of the duodenum, which connects to the stomach, the jejenum and the ileum, which connects with the large intestine. Related to image 3389.

On the left, the boundary of a breast tumor (yellow) attaches to collagen fibers that are closest to it (green) using DDR2. On the right, a tumor without DDR2 remains disconnected from the collagen.

Cells walk along body surfaces via tiny "feet," called focal adhesions, that connect with the extracellular matrix. See image 2502 for an unlabeled version of this illustration.

This tropical scene, reminiscent of a postcard from Key West, is actually a petri dish containing an artistic arrangement of genetically engineered bacteria. The image showcases eight of the fluorescent proteins created in the laboratory of the late Roger Y. Tsien, a cell biologist at the University of California, San Diego. Tsien, along with Osamu Shimomura of the Marine Biology Laboratory and Martin Chalfie of Columbia University, share the 2008 Nobel Prize in chemistry for their work on green fluorescent protein-a naturally glowing molecule from jellyfish that has become a powerful tool for studying molecules inside living cells.

Cells progress through a cycle that consists of phases for growth (blue, green, yellow) and division (red). Cells become quiescent when they exit this cycle (purple). See image 2499 for a labeled version of this illustration.

Multiphoton fluorescence image of HeLa cells with cytoskeletal microtubules (magenta) and DNA (cyan). Nikon RTS2000MP custom laser scanning microscope. See related images 3518, 3519, 3521, 3522.

The interior of a regenerating lizard tail 14 days after the original tail was amputated. Cell nuclei (blue), proliferating cells (green), cartilage (red), and muscle (white) have been visualized with immunofluorescence staining.

This image captures Purkinje cells (red), one of the main types of nerve cell found in the brain. These cells have elaborate branching structures called dendrites that receive signals from other nerve cells.

This image was part of the Life: Magnified exhibit that ran from June 3, 2014, to January 21, 2015, at Dulles International Airport.

Individual cells are color-coded based on their identity and signaling activity using a protein circuit technology developed by the Coyle Lab. Just as a radio allows you to listen to an individual frequency, this technology allows researchers to tune into the specific “radio station” of each cell through genetically encoded proteins from a bacterial system called MinDE. The proteins generate an oscillating fluorescent signal that transmits information about cell shape, state, and identity that can be decoded using digital signal processing tools originally designed for telecommunications. The approach allows researchers to look at the dynamics of a single cell in the presence of many other cells.

Related to image 7021.

This eerily glowing blob isn't an alien or a creature from the deep sea--it's a mouse embryo just eight and a half days old. The green shell and core show a protein called Smad4. In the center, Smad4 is telling certain cells to begin forming the mouse's liver and pancreas. Researchers identified a trio of signaling pathways that help switch on Smad4-making genes, starting immature cells on the path to becoming organs. The research could help biologists learn how to grow human liver and pancreas tissue for research, drug testing and regenerative medicine. In addition to NIGMS, NIH's National Institute of Diabetes and Digestive and Kidney Diseases also supported this work.

This image shows neonatal mouse heart cells. These cells were grown in the lab on a chip that aligns the cells in a way that mimics what is normally seen in the body. Green shows the muscle protein toponin I. Red indicates the muscle protein actin, and blue indicates the cell nuclei. The work shown here was part of a study attempting to grow heart tissue in the lab to repair damage after a heart attack. Image and caption information courtesy of the California Institute for Regenerative Medicine. Related to images 3281 and 3282.

Jellyfish are especially good models for studying the evolution of embryonic tissue layers. Despite being primitive, jellyfish have a nervous system (stained green here) and musculature (red). Cell nuclei are stained blue. By studying how tissues are distributed in this simple organism, scientists can learn about the evolution of the shapes and features of diverse animals.

This image was part of the Life: Magnified exhibit that ran from June 3, 2014, to January 21, 2015, at Dulles International Airport.

A light microscope image of a cell from the endosperm of an African globe lily (Scadoxus katherinae). This is one frame of a time-lapse sequence that shows cell division in action. The lily is considered a good organism for studying cell division because its chromosomes are much thicker and easier to see than human ones. Staining shows microtubules in red and chromosomes in blue. Here, condensed chromosomes are clearly visible and are starting to separate to form two new cells.

A light microscope image of cells from the endosperm of an African globe lily (Scadoxus katherinae). This is one frame of a time-lapse sequence that shows cell division in action. The lily is considered a good organism for studying cell division because its chromosomes are much thicker and easier to see than human ones. Staining shows microtubules in red and chromosomes in blue. Here, two cells have formed after a round of mitosis.

Related to images 1010, 1011, 1012, 1013, 1014, 1015, 1016, 1017, 1018, and 1021.

Muscles stretch and contract when we walk, and skin splits open and knits back together when we get a paper cut. To study these contractile forces, researchers built a three-dimensional scaffold that mimics tissue in an organism. Researchers poured a mixture of cells and elastic collagen over microscopic posts in a dish. Then they studied how the cells pulled and released the posts as they formed a web of tissue. To measure forces between posts, the researchers developed a computer model. Their findings--which show that contractile forces vary throughout the tissue--could have a wide range of medical applications.

Fruit fly sperm cells glow bright green when they express the gene for green fluorescent protein (GFP).

A mouse liver glows after being tagged with specially designed infrared-fluorescent protein (IFP). Since its discovery in 1962, green fluorescent protein (GFP) has become an invaluable resource in biomedical imaging. But because of its short wavelength, the light that makes GFP glow doesn't penetrate far in whole animals. So University of California, San Diego cell biologist Roger Tsien--who shared the 2008 Nobel Prize in chemistry for groundbreaking work with GFP--made infrared-fluorescent proteins (IFPs) that shine under longer-wavelength light, allowing whole-body imaging in small animals.

Cross-section of skin anatomy shows layers and different tissue types.

This illustration shows pathogenic bacteria behave like a Trojan horse: switching from antibiotic susceptibility to resistance during infection. Salmonella are vulnerable to antibiotics while circulating in the blood (depicted by fire on red blood cell) but are highly resistant when residing within host macrophages. This leads to treatment failure with the emergence of drug-resistant bacteria.

This image was chosen as a winner of the 2016 NIH-funded research image call, and the research was funded in part by NIGMS.

Cells move forward with lamellipodia and filopodia supported by networks and bundles of actin filaments. Proper, controlled cell movement is a complex process. Recent research has shown that an actin-polymerizing factor called the Arp2/3 complex is the key component of the actin polymerization engine that drives amoeboid cell motility. ARPC3, a component of the Arp2/3 complex, plays a critical role in actin nucleation. In this photo, the ARPC3-/- fibroblast cells were fixed and stained with Alexa 546 phalloidin for F-actin (red), Arp2 (green), and DAPI to visualize the nucleus (blue). Arp2, a subunit of the Arp2/3 complex, is absent in the filopodi-like structures based leading edge of ARPC3-/- fibroblasts cells. Related to images 3328, 3330, 3331, 3332, and 3333.

Undifferentiated embryonic stem cells cease to exist a few days after conception. In this image, ES cells are shown to differentiate into sperm, muscle fiber, hair cells, nerve cells, and cone cells.

Luciferase-based imaging enables visualization and quantification of internal organs and transplanted cells in live adult zebrafish. In this image, a cardiac muscle-restricted promoter drives firefly luciferase expression. This is the lateral and overhead (Bottom) view.
For imagery of the overhead view go to 3557.
For imagery of the lateral view go to 3558.
For more information about the illumated area go to 3559.

Influenza (flu) virus proteins in the act of self-replication. Viral nucleoprotein (blue) encapsidates [encapsulates] the RNA genome (green). The influenza virus polymerase (orange) reads and copies the RNA genome. In the background is an image of influenza virus ribonucleoprotein complexes observed using cryo-electron microscopy. This image is from a November 2012 News Release.

A light microscope image of a cell from the endosperm of an African globe lily (Scadoxus katherinae). This is one frame of a time-lapse sequence that shows cell division in action. The lily is considered a good organism for studying cell division because its chromosomes are much thicker and easier to see than human ones. Staining shows microtubules in red and chromosomes in blue. Here, condensed chromosomes are clearly visible near the end of a round of mitosis.

Related to images 1010, 1011, 1012, 1013, 1014, 1015, 1016, 1017, 1019, and 1021.

The membrane that surrounds a cell is made up of proteins and lipids. Depending on the membrane's location and role in the body, lipids can make up anywhere from 20 to 80 percent of the membrane, with the remainder being proteins. Cholesterol (green), which is not found in plant cells, is a type of lipid that helps stiffen the membrane.

On top, the brain of a sleep-deprived fly glows orange because of Bruchpilot, a communication protein between brain cells. These bright orange brain areas are associated with learning. On the bottom, a well-rested fly shows lower levels of Bruchpilot, which might make the fly ready to learn after a good night's rest.

Shiga toxin (green) is sorted from the endosome into membrane tubules (red), which then pinch off and move to the Golgi apparatus.

In this image, viewed with a ZEISS ORION NanoFab microscope, the community of cells lining a mouse airway is magnified more than 10,000 times. This collection of cells, known as the mucociliary escalator, is also found in humans. It is our first line of defense against inhaled bacteria, allergens, pollutants, and debris. Malfunctions in the system can cause or aggravate lung infections and conditions such as asthma and chronic obstructive pulmonary disease. The cells shown in gray secrete mucus, which traps inhaled particles. The colored cells sweep the mucus layer out of the lungs.

This image was part of the Life: Magnified exhibit that ran from June 3, 2014, to January 21, 2015, at Dulles International Airport.

This graphic that resembles a firework was created from a picture of a fruit fly spermatid. This fruit fly spermatid recycles various molecules, including malformed or damaged proteins. Actin filaments (red) in the cell draw unwanted proteins toward a barrel-shaped structure called the proteasome (green clusters), which degrades the molecules into their basic parts for re-use.

The nucleus of a human fibroblast cell with chromatin—a substance made up of DNA and proteins—shown in various colors. Fibroblasts are one of the most common types of cells in mammalian connective tissue, and they play a key role in wound healing and tissue repair. This image was captured using Stochastic Optical Reconstruction Microscopy (STORM).

Related to images 6888 and 6893.

Floral pattern emerging as two bacterial species, motile Acinetobacter baylyi and non-motile Escherichia coli (green), are grown together for 72 hours on 0.5% agar surface from a small inoculum in the center of a Petri dish.

See 6557 for a photo of this process at 24 hours on 0.75% agar surface.
See 6553 for a photo of this process at 48 hours on 1% agar surface.
See 6555 for another photo of this process at 48 hours on 1% agar surface.
See 6550 for a video of this process.

A peripheral nerve cell made from human embryonic stem cell-derived neural crest stem cells. The nucleus is shown in blue, and nerve cell proteins peripherin and beta-tubulin (Tuj1) are shown in green and red, respectively. Related to image 3263.

The 3D single-molecule super-resolution reconstruction of the entire nuclear lamina in a HeLa cell was acquired using the TILT3D platform. TILT3D combines a tilted light sheet with point-spread function (PSF) engineering to provide a flexible imaging platform for 3D single-molecule super-resolution imaging in mammalian cells.
See 6573 for 3 separate views of this structure.

A genetic disorder of the nervous system, neurofibromatosis causes tumors to form on nerves throughout the body, including a type of tumor called an optic nerve glioma that can result in childhood blindness. The image was used to demonstrate the unique imaging capabilities of one of our newest (at the time) laser scanning microscopes and is of a wildtype (normal) mouse retina in the optic fiber layer. This layer is responsible for relaying information from the retina to the brain and was fluorescently stained to reveal the distribution of glial cells (green), DNA and RNA in the cell bodies of the retinal ganglion neurons (orange) and their optic nerve fibers (red), and actin in endothelial cells surrounding a prominent branching blood vessel (blue). By studying the microscopic structure of normal and diseased retina and optic nerves, we hope to better understand the altered biology of the tissues in these tumors with the prospects of developing therapeutic interventions.

Hepatocytes, like the one shown here, are the most abundant type of cell in the human liver. They play an important role in building proteins; producing bile, a liquid that aids in digesting fats; and chemically processing molecules found normally in the body, like hormones, as well as foreign substances like medicines and alcohol.

This image was part of the Life: Magnified exhibit that ran from June 3, 2014, to January 21, 2015, at Dulles International Airport.

This video condenses 6.5 minutes into less than a minute to show how the toxin in bee venom, called melittin, destroys an animal or bacterial cell. What looks like a red balloon is an artificial cell filled with red dye. Melittin molecules are colored green and float on the cell's surface like twigs on a pond. As melittin accumulates on the cell's membrane, the membrane expands to accommodate it. In the video, the membrane stretches into a column on the left. When melittin levels reach a critical threshold, countless pinhole leaks burst open in the membrane. The cell's vital fluids (red dye in the video) leak out through these pores. Within minutes, the cell collapses.

The molecules that glow blue in these cultured cells prevent the expression of the mutant proteins that cause Huntington's disease. Biochemist David Corey and others at UT Southwestern Medical Center designed the molecules to specifically target the genetic repeats that code for harmful proteins in people with Huntington's disese. People with Huntington's disease and similar neurodegenerative disorders often have extra copies of a gene segment. Moving from cell cultures to animals will help researchers further explore the potential of their specially crafted molecule to treat brain disorders. In addition to NIGMS, NIH's National Institute of Neurological Disorders and Stroke and National Institute of Biomedical Imaging and Bioengineering also funded this work.