MICROSCOPY RESEARCH AND TECHNIQUE 44:311 (1999)
Introduction to Use of Atomic Force Microscopy
and Optical Tweezers in Biology
In this topical issue entitled ‘‘Use of Atomic Force
Microscopy and Optical Tweezers in Biology,’’ various
applications of the Atomic Force Microscope (AFM) and
Optical Tweezers for the study of cellular and biomolecu-
lar structure and function have been examined. Until
recently, our current understanding of the structure
and function of cells and biomolecules has been ob-
tained from studies using light and electron micro-
scopes. Since, optical resolution is limited by the wave-
length of light used (0.25–3 µm), and structural
alterations may result from fixation and drying re-
quired for electron microscopy, the AFM can be used in
the study of live cells and hydrated biological samples.
In the last decade, the AFM has demonstrated its
capability of imaging live cells and biological samples in
fluid, at nanometer resolution. The AFM has also been
used as a force spectroscope to study molecular interac-
tions between biomolecules in fluid. Similarly, in the
last few years, optical trapping of small biological
particles using forces of laser radiation pressure has
been used for protein-protein and molecular interaction
studies. Both AFM and the Optical Tweezers have been
found to be capable of measuring biophysical properties
such as intermolecular forces of up to 0.2 pN.
Besides providing examples of the application of AFM
and Optical Tweezers in the study of cellular and
biomolecular structure and function, the present issue
provides some technical advancements in their use. In
the first article, by Taatjes et al., assessment of AFM
probes prior to their use in obtaining images of biologi-
cal samples in fluid, have been elegantly demonstrated.
Similarly, in the last article of this issue, the Optical
Tweezer is used as a ‘‘Photonic Force Microscope’’ to
study the three-dimensional tracking of GPI-anchored
membrane proteins in live hippocampal neurons in
physiological buffer.
The biggest advantage of examining cells and biologi-
cal material by the AFM, is its ability to examine
objects in fluid. In the study by Freund et al., the
hydration states of samples have been examined using
AFM. Information from such studies is critical in
understanding the level of hydration of cellular and
subcellular organelles. The influence of hydration lev-
els of a biological substance on the image generated by
the AFM can now be critically evaluated and assessed.
In studies by Schmidt et al., fluorescence microscopy in
combination with AFM has been employed to study
r 1999 WILEY-LISS, INC.
biodynamics at the single molecule level. Following this
manuscript, studies on biomolecular complexes have
been examined using the AFM. In the study by Taatjes
et al., Type III collagen was examined in buffer at high
resolution by the AFM. The dynamics of the formation
of mature collagen fibrils from reconstituted collagen
was studied. Results from this study will help us
understand the molecular interaction of Type III colla-
gen in blood vessels. The next study by Malghani et al.
demonstrates the self-assembly of heptameric ␣-hemo-
lysin in lipid membranes, using the AFM. The study by
Fritzsche, describes how the AFM can be used to study
the volume of isolated chromosomes. Slezak et al. use
AFM as a force spectroscope, to understand the binding
interactions between microsomal membrane and the
plasma membrane in rat livers obtained from normal
and pancreatitic animals. This study demonstrates the
use of AFM to investigate altered membrane binding
kinetics in diseased animals. In the study by Ellis et al.,
the AFM has been used both as an imaging tool and a
force spectroscope.
It is difficult to cover two entire fields in a single
issue. However, we feel that the studies described here
give a good across-the-board flavor for the use of the
AFM and the Optical Tweezer for biological applica-
tions. It is our hope that, after examining this collection
of papers, the reader will become as excited as we are
about the use of both these cutting-edge techniques and
can envision the advantages of employing them in their
own studies.
BHANU P. JENA (Guest Editor)
Department of Surgery &
Biomedical Engineering Program
Yale University School of Medicine,
New Haven, CT, USA
JOHN GEIBEL (Assoc. Guest Editor)
Department of Surgery & Molecular &
Cellular Physiology
Yale University School of Medicine,
New Haven, CT, USA
STEFAN W. SCHNEIDER (Assoc. Guest Editor)
Vegetative Physiologie
Robert Koch Str. 27a (Innenhof)
48149 Muenster, Germany