Understanding the intricate relationship between macromolecular structure and function represents a central goal of undergraduate biology education (1–3). In teaching complex three-dimensional (3D) concepts, instructors typically depend on static two-dimensional (2D) textbook images or computer-based visualization software, which can lead to unintended misconceptions (4–6). While chemical and molecular kits exist, these models cannot handle the size and detail of macromolecules. Consequently, students may graduate in the life sciences without understanding how structure underlies function or acquiring skills to translate between 2D and 3D molecular models (5, 7)

Booth, Christine S.

Couch, Brian A.

Helikar, Tomáš

Howell, Michelle E.

Roston, Rebecca

van Dijk, Karin V.

English

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University of Nebraska - Lincoln
DigitalCommons@University of Nebraska - Lincoln
Biochemistry -- Faculty Publications Biochemistry, Department of
2018
Visualizing the Invisible: A Guide to Designing,
Printing, and Incorporating Dynamic 3D
Molecular Models to Teach Structure–Function
Relationships
Michelle E. Howell
University of Nebraska - Lincoln, michelle.palmer@unl.edu
Karin V. van Dijk
University of Nebraska - Lincoln, kvandijk2@unl.edu
Christine S. Booth
University of Nebraska-Lincoln, christine.b2@gmail.com
Tomáš Helikar
University of Nebraska–Lincoln, thelikar2@unl.edu
Brian A. Couch
University of Nebraska - Lincoln, bcouch2@unl.edu
See next page for additional authorsFollow this and additional works at: https://digitalcommons.unl.edu/biochemfacpub
Part of the Biochemistry Commons, Biotechnology Commons, and the Other Biochemistry,
Biophysics, and Structural Biology Commons
This Article is brought to you for free and open access by the Biochemistry, Department of at DigitalCommons@University of Nebraska - Lincoln. It
has been accepted for inclusion in Biochemistry -- Faculty Publications by an authorized administrator of DigitalCommons@University of Nebraska -
Lincoln.
Howell, Michelle E.; van Dijk, Karin V.; Booth, Christine S.; Helikar, Tomáš; Couch, Brian A.; and Roston, Rebecca, "Visualizing the
Invisible: A Guide to Designing, Printing, and Incorporating Dynamic 3D Molecular Models to Teach Structure–Function
Relationships" (2018). Biochemistry -- Faculty Publications. 408.
https://digitalcommons.unl.edu/biochemfacpub/408
Authors
Michelle E. Howell, Karin V. van Dijk, Christine S. Booth, Tomáš Helikar, Brian A. Couch, and Rebecca
Roston
This article is available at DigitalCommons@University of Nebraska - Lincoln: https://digitalcommons.unl.edu/biochemfacpub/408
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DOI: https://doi.org/10.1128/jmbe.v19i3.1663
Tips & Tools
Journal of Microbiology & Biology Education  1Volume 19, Number 3
©2018 Author(s). Published by the American Society for Microbiology.  This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial-NoDerivatives 4.0 International 
license (https://creativecommons.org/licenses/by-nc-nd/4.0/ and https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode), which grants the public the nonexclusive right to copy, distribute, or display the published work. 
*Corresponding authors. Dr. Brian A. Couch. Mailing address: 
School of Biological Sciences, University of Nebraska, 204 Manter 
Hall, Lincoln, NE 68588-0118. Phone: 402-472-8130. 
E-mail: bcouch2@unl.edu. Dr. Rebecca L. Roston. 
Mailing address: Department of Biochemistry, University of 
Nebraska, N123 Beadle Center, Lincoln, NE 68588-0664. 
Phone: 402-472-2936. E-mail: rroston@unl.edu.
Received: 24 July 2018, Accepted: 13 September 2018, Published: 
31 October 2018.
†Supplemental materials available at http://asmscience.org/jmbe
INTRODUCTION
Understanding the intricate relationship between mac-
romolecular structure and function represents a central 
goal of undergraduate biology education (1–3). In teaching 
complex three-dimensional (3D) concepts, instructors 
typically depend on static two-dimensional (2D) textbook 
images or computer-based visualization software, which can 
lead to unintended misconceptions (4–6). While chemical 
and molecular kits exist, these models cannot handle the 
size and detail of macromolecules. Consequently, students 
may graduate in the life sciences without understanding how 
structure underlies function or acquiring skills to translate 
between 2D and 3D molecular models (5, 7).
Building on recent technological advances, 3D printing 
(3DP) potentiates an era in which students learn through 
direct interaction with dynamic 3D structural models. With 
3DP, instructors have the opportunity to use tailor-made 
models of virtually any size molecule. For example, protein 
models can be designed to relate enzyme active site struc-
tures to kinetic activity. Furthermore, instructors can use 
diverse printing materials and accessories to demonstrate 
molecular properties, dynamics, and interactions (Fig. 1). In 
this article and supplemental guide, we present an example 
of how to incorporate a 3D model-based lesson on DNA 
supercoiling in an undergraduate biochemistry classroom 
and best practices for designing and printing 3D models. 
PROCEDURE
Classroom integration
To address learning goals related to DNA structure 
and function, we designed and printed flexible plastic 
models with magnetic ends to mimic DNA supercoiling 
(Appendices 1 and 2). We selected this model material 
so students could feel DNA relaxation and witness con-
tortions resulting from twists in DNA. We developed 
a Qualtrics-based interactive activity to help students 
use the models to classify supercoiled DNA, predict 
the effects of DNA wrapping around nucleosomes, and 
Visualizing the Invisible: A Guide to Designing, Printing, and Incorporating 
Dynamic 3D Molecular Models to Teach Structure–Function Relationships †
Michelle E. Howell1,2, Karin van Dijk1, Christine S. Booth1, Tomáš Helikar1, Brian A. Couch2*,  
and Rebecca L. Roston1*
1Department of Biochemistry, University of Nebraska, Lincoln, NE 68588-0664;  
2School of Biological Sciences, University of Nebraska, Lincoln, NE 68588-0118
FIGURE 1. A selection of 3D models with interactive features. 
A) The Enterobacteria phage λ transcription factor has interchange-
able amino acids that allow investigation of point mutations on DNA 
binding. B) A DNA helix with LEGO-style replaceable base pairs 
allows investigation of DNA mutations. Models in A and B can be 
used together to allow investigation of compensatory mutations. 
Multicolored, detailed models of a DNA helix (C) or protein α-helix 
and water molecule (D) allow investigation of chemical details, for 
example, the size of the major and minor grooves or the diameter 
of the inside of a helix. Flexible models of Phe-tRNA (E), single-
stranded RNA and DNA (F), and a long DNA duplex with magnetic 
ends (G) allow students to engage with the molecular dynamics, 
investigating folding of complex structures and demonstrating 
chemical attack, base stacking, or DNA supercoiling. 
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Journal of Microbiology & Biology Education  
HOWELL et al.: DESIGNING, PRINTING, AND TEACHING WITH 3D MOLECULAR MODELS
Volume 19, Number 32
differentiate between topoisomerase activities (Fig. 2). 
We divided an upper-level undergraduate biochemistry 
lecture class into groups of two to three students to fos-
ter peer-learning, and we provided each group with one 
model set. The models were also made available at our 
library resource center. Interactive questions required 
students to measure and explore physical aspects of the 
models. It took students roughly 50 minutes to complete 
the activity during class, and it was interspersed with lec-
ture and demonstration via a digital overhead. Alternative 
deployments and tips for effective model implementa-
tion in a variety of course formats are outlined in Figure 
3. Students reported in interviews that models were 
valuable for their learning because “physically seeing it 
makes something abstract very real.” In a survey, 60 to 
70 percent of students agreed that physical models made 
it easier to learn the material being taught. 
Making 3D models
We designed our 3DP models around student mis-
conceptions. Misconceptions regarding chemical struc-
ture were addressed with precise molecular replicas, 
and misconceptions about molecular interactions were 
addressed with simplified models that could replicate 
movement. A step-by-step video and text guide for our 
design of a flexible DNA model are provided as an ex-
ample (Appendices 1 and 2 and https://digitalcommons.
unl.edu/structuralmodels/22).
Numerous free online software programs and tuto-
rials exist to facilitate designing 3D models. Molecular 
coordinates for thousands of macromolecules are housed 
in the Protein Data Bank and Nucleic Acid Data Bank. To 
print all or part of a macromolecule, start by download-
ing and opening the molecular coordinates in a molecular 
visualization software program, such as PyMOL or Chi-
mera, then adjust the molecule’s size, color, thickness, and 
representation (e.g., ball-and-stick, ribbon, space-filling). 
Finally, export the structure to a graphics program, such 
as Blender or MeshLab, to add LEGO-style attachments 
(Figs. 1A and B), holes for magnets (Fig. 2), or other 
design elements. Alternatively, a simplified model can 
be built de novo using these same graphics programs and 
piecing together various shapes, as we did for the DNA 
supercoiling model (Fig. 2). 
Following the design process, the object coordinates 
must be exported in a file format that can be read by a 
3D printer, such as .stl or .x3d (8). Because most mac-
romolecules lack a broad base that completely supports 
the structure, a type of 3DP called selective laser sintering 
(SLS) produces the best results. It utilizes a growing bed 
of powder to support otherwise unsupported parts of 
the model being printed. For each layer, a CO2 laser beam 
fuses the powder in a specific 2D pattern according to the 
design file. This process repeats across the entire model 
as each layer is successively fused to the previous layer; 
the unbound powder is then blown away, leaving the fused 
product (9). While SLS printers are cost-prohibitive, cost-
effective SLS printing is accessible through various online 
printing services, such as Shapeways (http://shapeways.com), 
where our typical models cost between $5 and $30 (Figs. 1 
and 2). Three-dimensional printing services offer numerous 
printing substrates, including a variety of plastics, metals, 
and sandstone. While plastics are durable and can be flex-
ible, they are one color. Sandstone is a low-cost multicolor 
FIGURE 2. Investigating DNA supercoiling. In step 1, students 
wrapped the DNA model (white) around a nucleosome model (blue) 
and characterized the resulting supercoil. In steps 2–4, students 
mimicked Topoisomerase II by cleaving the DNA and passing the 
intact strand of DNA through the cleaved site before re-adhering 
the ends. In step 5, students characterized the resulting supercoil 
and evaluated Topoisomerase II activity.
FIGURE 3. Course integration of 3D instructional models. Integra-
tion tips are outlined for in-class activities (blue sequence), in-class 
demonstrations (teal sequence), and out-of-class homework (green 
sequence). 1 Based on cognitive theory of multimedia learning (11), 
instructors are recommended to include 2D and 3D models in addi-
tion to lecture. 2 For small classes, a one-on-one interaction with the 
instructor is preferred; for large classes or homework assignments, 
an adaptive response-guided activity can be substituted. 3 Formative 
assessments can provide instant feedback if they include in-class 
questions. UG = undergraduate; HS = high school.
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Journal of Microbiology & Biology Education  
HOWELL et al.: DESIGNING, PRINTING, AND TEACHING WITH 3D MOLECULAR MODELS
3Volume 19, Number 3
material, but resulting models are brittle and need to be 
clear-coated to increase their strength. Some print services 
offer a coated sandstone option, or clear epoxy can be ap-
plied after printing. Metals are stronger than plastic but are 
rigid and more expensive. 
Most personal 3D printers extrude plastic from a 
movable source, slowly building a 3D model in a process 
referred to as fused deposition modeling (FDM). Although 
more time consuming, FDM can produce accurate 3D 
macromolecules if a support matrix can be printed that 
can be dissolved upon print completion. Personal 3D 
printers are usually highly cost effective, especially if 
the machine and expertise are already available, though 
materials are limited by the printer’s capabilities. Note 
that all 3D printers have potential environmental and 
health risks, including toxic nanoparticle and chemical 
vapor emissions, as well as heat, electrical, and mechani-
cal risks, so users should consider the health risks of the 
materials used and consult their owner’s manual for safe 
operating procedures (10). 
Instructors can freely download the printer files and 
print any of the custom 3D macromolecular models we 
developed and tested with students (Fig. 1; https://digital 
commons.unl.edu/structuralmodels/ or https://3dprint.
nih.gov/discover) or inexpensively purchase (at no profit 
to ourselves) the corresponding models at www.shape 
ways.com/shops/macromolecules. We encourage use 
or adaptation of these models as needed. Please review 
these repositories for future developments and contact 
us with questions. 
CONCLUSION
Three-dimensional printing represents an emerging 
technology with significant potential to advance life-science 
education by allowing students to physically explore mac-
romolecular structure-function relationships and observe 
molecular dynamics and interactions. As this technology 
develops, the cost, resolution, strength, material options, 
and convenience of 3DP will improve, making 3D models 
an even more accessible teaching tool. While instructors 
who wish to design their own models potentially face a 
learning curve, this report and accompanying guide lay out 
the basic steps and considerations needed to start designing 
and printing 3D models. 
SUPPLEMENTAL MATERIALS
Appendix 1: Video guide to design flexible DNA
Appendix 2: Video transcript and directions
ACKNOWLEDGMENTS
This work was supported by National Science Founda-
tion grant # NSF DUE-1625804. The authors declare that 
there are no conflicts of interest. 
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Visualizing the Invisible: A Guide to Designing, Printing, and Incorporating
Dynamic 3D Molecular Models to Teach Structure–Function Relationships

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Visualizing the Invisible: A Guide to Designing, Printing, and Incorporating Dynamic 3D Molecular Models to Teach Structure–Function Relationships

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