The past four decades have seen many advances in electron microscopy at Arizona State University, and Ray Carpenter has been instrumental in many of them.

After a productive 13 years at Oak Ridge National Laboratory, Carpenter came to ASU in 1980 as a tenured full professor and the founding director of the NSF National Facility for High Resolution Electron Microscopy in the interdisciplinary Center for Solid State Science. Ray Carpenter reflects on his ASU career. Download Full Image

Last week, Carpenter gathered with colleagues, former students, friends and family at ASU’s University Club to celebrate his career.

“When I look back over my career, I have to say my whole time at ASU has been quite memorable," said the professor in the School of Molecular Sciences and the Eyring Materials Center. "Through the center and its Winter Schools program and research conferences, I have interacted and worked with internally known researchers who are quite prominent experts in the electron microscopy/solid state science world. Being able to interact with such a large group of accomplished scientists, engineers and students with such strong common interests is a memorable event spanning decades.”

Carpenter’s career has also been remarkable. He took the lead in helping ASU acquire two aberration-corrected electron microscopes, which were funded by a large Major Research Instrumentation grant from the National Science Foundation. Installation of these instruments was no small feat as it required the design and construction of a building without stray magnetic or electric fields, nor mechanical or acoustic vibrations that would distort images and degrade resolution.

“The measured stage drift rates of both microscopes were about 1,000 times less than continental drift rates, which is quite remarkable,” Carpenter said. “These microscopes made atomic resolution straightforward and continue to produce striking research results.”

In addition to research, Carpenter enjoyed teaching students practical applications of electron microscopy. Carpenter, with longtime colleague David Smith, developed and taught a comprehensive Transmission Electron Microscope (TEM) course with applications to physics, chemistry, geology and materials science.

“When I joined ASU, the dean of engineering requested that I teach a microscopy class that was useful to engineers,” Carpenter said. “The course, which included an emphasis on applications to materials problems, began as a one-semester lecture class. With the help of Professor Dave Smith, the course expanded to fall and spring lecture classes with three-credit laboratory classes with hands-on microscope for students, totaling 12 credits in microscopy.”

David Smith, who taught the second-semester TEM class, said, “Hundreds of students have taken Ray’s TEM class, and many of them now hold faculty positions not only around this country, but also around the world. These classes became the most comprehensive electron-microscopy courses in the country, if not the world. Many of our microscopy students have also gone on to distinguished careers in national labs and industry.”

Carpenter has been active at many levels throughout the university, including serving as director of the Center for Solid State Science, and chairing and serving on many PhD committees. Carpenter was also the founding director of the Science and Engineering of Materials graduate program. His many accomplishments were recognized with the ASU Faculty Achievement Award in 1990.

Outside of ASU, Carpenter has been active in several professional societies throughout his career, primarily the Microscopy Society of America, where he is a member of the inaugural class of elected fellows. Carpenter also served as director of Physical Sciences of the Microscopy Society of America, and he was later elected as its president.

Retirement for Carpenter will include some continued research at ASU but will incorporate more time with family and traveling.

“I enjoy family gatherings during holiday, birthdays and other celebrations,” Carpenter said. “I look forward to enjoying our national parks and events like chuckwagon cookouts and dude ranches. There are lots of things to do.” 

Science writer, School of Molecular Sciences

480-965-2729 Klem@asu.edu

Just as countries import a vast array of consumer goods across national borders, so living cells are engaged in a lively import-export business.Their ports of entry are sophisticated transport channels embedded in a cell’s protective membrane. Regulating what kinds of cargo can pass through the borderlands formed by the cell’s two-layer membrane is essential for proper functioning and survival...

Just as countries import a vast array of consumer goods across national borders, so living cells are engaged in a lively import-export business.

Their ports of entry are sophisticated transport channels embedded in a cell’s protective membrane. Regulating what kinds of cargo can pass through the borderlands formed by the cell’s two-layer membrane is essential for proper functioning and survival. Graphic shows the bilayer structure of a living cell membrane, composed of phospholipid. A phospholipid consists of a hydrophilic, or water-loving, head and hydrophobic, or water-fearing, tail. The hydrophobic tails are sandwiched between two layers of hydrophilic heads. At the center, a channel is shown, permitting the transport of biomolecules. Download Full Image

In new research, Arizona State University Professor Hao Yan, along with ASU colleagues and international collaborators from University College London describe the design and construction of artificial membrane channels, engineered using short segments of DNA. The DNA constructions behave much in the manner of natural cell channels or pores, offering selective transport of ions, proteins and other cargo, with enhanced features unavailable in their naturally occurring counterparts.

These innovative DNA nanochannels may one day be applied in diverse scientific domains, ranging from biosensing and drug delivery applications to the creation of artificial cell networks capable of autonomously capturing, concentrating, storing and delivering microscopic cargo.

“Many biological pores and channels are reversibility gated to allow ions or molecules to pass through,” Yan says. "Here, we emulate these nature processes to engineer DNA nanopores that can be locked and opened in response to external 'key' or 'lock' molecules.”

Yan is the Milton D. Glick Distinguished Professor in Chemistry and Biochemistry at ASU and directs the Biodesign Center for Molecular Design and Biomimetics. He is also a professor with ASU’s School of Molecular Sciences.

The research findings appear in the current issue of the journal Nature Communications.

All living cells are enveloped in a unique biological structure: the cell membrane. The "science-y" term for such membranes is phospholipid bilayer, meaning the membrane is formed from phosphate molecules attached to a fat, or lipid, component to form an outer and inner membrane layer (see image above).

These inner and outer membrane layers are a bit like a room’s inner and outer walls. But unlike normal walls, the space between inner and outer surfaces is fluid, resembling a sea. Further, cell membranes are said to be semipermeable, allowing designated cargo entry or exit from the cell. Such transport typically occurs when the transiting cargo binds with another molecule, altering the dynamics of the channel structure to permit entry into the cell, somewhat like the opening of the Panama Canal.

Semipermeable cell membranes are necessary for protecting sensitive ingredients within the cell from a hostile environment outside, while allowing the transit of ions, nutrients, proteins and other vital biomolecules. Hao Yan is the Milton D. Glick Distinguished Professor in Chemistry and Biochemistry at ASU and directs the Biodesign Center for Molecular Design and Biomimetics. He is also a professor with ASU’s School of Molecular Sciences.

Hao Yan is the Milton D. Glick Distinguished Professor in Chemistry and Biochemistry at ASU and directs the Biodesign Center for Molecular Design and Biomimetics. He is also a professor with ASU’s School of Molecular Sciences.

Researchers, including Yan, have explored the possibility of creating selective membrane channels synthetically, using a technique known as DNA nanotechnology.

The basic idea is simple. The double strands of DNA that form the genetic blueprint for all living organisms are held together through the base pairing of the molecule’s four nucleotides, labelled "A," "T," "C" and "G." A simple rule applies, namely that "A" nucleotides always pair with "T" and "C" always pair with "G." Thus, a DNA segment "ATTCTCG" would form a complementary strand with "CAAGAGC."

Base pairing of DNA allows the synthetic construction of a virtually limitless array of 2D and 3D nanostructures. Once a structure has been carefully designed, usually with the aid of computer, the DNA segments can be mixed together and will self-assemble in solution into the desired form.

Creating a semipermeable channel using DNA nanotechnology, however, has proven a vexing challenge. Conventional techniques have failed to replicate the structure, and capacities of nature-made membrane channels and synthetic DNA nanopores generally permit only one-way transport of cargo.

The new study describes an innovative method, allowing researchers to design and construct a synthetic membrane channel whose pore size permits the transport of larger cargo than natural cell channels can. Unlike previous efforts to create DNA nanopores affixed to membranes, the new technique builds the channel structure step-by-step, by assembling the component DNA segments horizontally with respect to the membrane, rather than vertically. The method permits the construction of nanopores with wider openings, allowing the transport of a greater range of biomolecules.

Further, the DNA design allows the channel to be selectively opened and closed by means of a hinged lid, equipped with a lock and key mechanism. The “keys” consist of sequence-specific DNA strands that bind with the channel’s lid and trigger it to open or close.

In a series of experiments, the researchers demonstrate the ability of the DNA channel to successfully transport cargo of varying sizes, ranging from tiny dye molecules to folded protein structures, some larger than the pore dimensions of natural membrane channels. 

The researchers used atomic force microscopy and transmission electron microscopy to visualize the resulting structures, confirming that they conformed to the original design specifications of the nanostructures.

Fluorescent dye molecules were used to verify that the DNA channels successfully pierced and inserted themselves through the cell’s lipid bilayer, successfully providing selective entry of transport molecules. The transport operation was carried out within one hour of channel formation, a significant improvement over previous DNA nanopores, which typically require five to eight hours for complete biomolecule transit.

The DNA nanochannels may be used to capture and study proteins and closely examine their interactions with the biomolecules they bind with, or to study the rapid and complex folding and unfolding of proteins. Such channels could also be used to exert fine-grained control over biomolecules entering cells, offering a new window on targeted drug delivery. Many other possible applications are likely to arise from the newfound ability to custom design artificial, self-assembling transport channels.

Science writer, Biodesign Institute at ASU

480-727-0378 richard.harth@asu.edu